Medical device, and method for producing same

ABSTRACT

A medical device includes a layer made of an acidic polymer and a basic polymer formed on at least a part of a surface of a base material, wherein at least one kind of an acidic polymer and a basic polymer forming the layers made of the acidic polymer and the basic polymer is a multi-component copolymer of three or more components.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is the U.S. National Phase Application of the PCTInternational Application No. PCT/JP2012/070704, filed Aug. 14, 2012,which claims priority to Japan Patent Application No. 2011-178664, filedAug. 17, 2011, the contents of each of these applications beingincorporated by reference herein in their entireties for all purposes.

FIELD OF THE INVENTION

The present invention relates to a medical device and a method forproducing the same

BACKGROUND OF THE INVENTION

As one of medical devices, a soft contact lens (a soft ophthalmic lens)is exemplified. In a commercially available soft contact lens, ahydrogel material having a water content of about 25% to about 80% isusually used. A water-containing soft contact lens made of a hydrogelmaterial, however, causes a phenomenon that water evaporates from thecontact lens because the contact lens contains water. By thisphenomenon, certain percentage of contact lens wearers may feel drynessstronger than when the wearers are naked eye and may feel uncomfortable.Some wearers who complain of symptoms called contact lens dry eye haveexisted. In addition, a water-containing soft contact lens made of ahydrogel material is easily contaminated with components in a lacrimalfluid and contains large amount of water, and therefore, the lens alsohas a risk of bacterial proliferation. Moreover, although a siliconehydrogel material, which is a hydrogel material further containing asilicone component, has high oxygen permeability, and lipid stainseasily adhere to the surface because the silicone component ishydrophobic. A problem that the lipid stain adhesion is not completelyimproved therefore arises even if a hydrophilic polymer such aspolyacrylic acid is coated.

On the other hand, as a low water content soft contact lenses havinghigh oxygen permeability, for example, a silicone rubber lens obtainedby a method in which a platinum catalyst is added to a mixture of apolydimethylsiloxane in which both molecular ends are blocked withvinylmethylsilyl groups and a methyl hydrogen polysiloxane and themixture is heated and cured by the molding method is known (PatentLiterature 1).

In addition, contact lens materials having high oxygen permeabilitymainly made of polysiloxane having a plurality of polymerizablefunctional groups are also described in Patent Literatures 2 to 6. Amongthese Patent Literatures, in Patent Literature 6, a contact lensmaterial made of a polymer obtained by polymerizing only bifunctionalorganic siloxane macromers or copolymerizing the macromers with othermonomers is disclosed. As the monomer used for the copolymerization, anacrylic acid fluoroalkyl ester or a methacrylic acid fluoroalkyl esterand an acrylic acid alkyl ester or a methacrylic acid alkyl ester aredisclosed.

However, in a conventional low water content soft contact lenses havinghigh oxygen permeability, the following problems are also observed. Thesilicone rubber lens described in Patent Literature 1 has disadvantagesthat a hydrophilic treatment layer that is provided for improving ahydrophobic property of a lens surface is peeled and that fixation to acornea occurs because of too large elasticity, and thus, has not beenwidely used in practical use.

The materials mainly made of a polysiloxane having a plurality ofpolymerizable functional groups described in Patent Literatures 2 to 6have high oxygen permeability as well as flexibility, and therefore, thematerials are considered as one of the materials suitable for a contactlens. However, the materials may cause fixation to a cornea becausetackiness remains on the lens surface after polymerization and the lenshas insufficient balance between flexibility and mechanical propertiessuch as folding resistance.

Various methods have been known with respect to a method for modifying asurface of a medical device. Among them, methods of coating two or morepolymer materials layer by layer and stacking the layers have been known(Patent Literatures 7 to 9). Among these methods, a method ofalternately coating polymer materials having two opposite charges layerby layer is called an LbL method. The layers of each material areconsidered to be bonded to other layers made of a different material ina noncovalent bonding manner. However, high oxygen permeability softophthalmic lenses in which usefulness of this method is clearlydescribed are only lenses made of a silicone hydrogel material andusefulness to a low water content soft ophthalmic lens has not beenknown. In addition, a conventional LbL coating has been carried out formany layers such as about 4 layers to about 20 layers, and therefore, aproduction process may become longer and a production cost may beincreased.

PATENT LITERATURE

-   Patent Literature 1: Japanese Patent Application Laid-open No.    54-81363-   Patent Literature 2: Japanese Patent Application Laid-open No.    54-24047-   Patent Literature 3: Japanese Patent Application Laid-open No.    56-51715-   Patent Literature 4: Japanese Patent Application Laid-open No.    59-229524-   Patent Literature 5: Japanese Patent Application Laid-open No.    2-188717-   Patent Literature 6: Japanese Patent Application Laid-open No.    5-5861-   Patent Literature 7: Japanese National Publication of International    Patent Application No. 2002-501211-   Patent Literature 8: Japanese National Publication of International    Patent Application No. 2005-538418-   Patent Literature 9: Japanese National Publication of International    Patent Application No. 2009-540369

SUMMARY OF THE INVENTION

The present invention is aimed at solving the problems described above.With respect to a low water content base material, the present inventionaims to provide a medical device that significantly reduces or avoids aphenomenon that a contact lens adheres to a cornea and the like at thetime of wearing the contact lens by improving wettability and alubricity, and reduces a risk of bacterial proliferation by improving anantifouling property to body fluids such as a lacrimal fluid. Inaddition, with respect to a water-containing base material, the presentinvention aims to provide a medical device having adequate wettabilityand lubricity and having excellent lipid adhesion resistance. Thepresent invention also aims to produce the medical device inexpensivelyby a simple process.

The present invention includes the following constitution.

A medical device according to an embodiment of the present inventionincludes a layer made of an acidic polymer and a basic polymer formed onat least a part of a surface of a base material, wherein at least onekind of an acidic polymer and a basic polymer forming the layer made ofthe acidic polymer and the basic polymer is a multi-component copolymerof three or more components.

In the above, it is preferable that the layer made of the acidic polymerand the basic polymer is formed by carrying out treatment with one ormore kinds of an acidic polymer solution one or more times and carryingout treatment with one or more kinds of a basic polymer solution one ormore times.

Moreover, in the above, it is preferable for the present invention thatthe multi-component copolymer of three or more components comprises oneor more kinds of each of an acidic monomer or a basic monomer, a monomerhaving a hydroxy group, and a monomer having an amide group.

One preferable aspect of the present invention provides a method forproducing a medical device including the following step 1 to step 4 inthis order:

<Step 1>

polymerizing a mixture including a monomer having a siloxanyl group toobtain a molding;

<Step 2>

contacting the molding to an acidic polymer solution, and thereafter,washing and removing the excessive acidic polymer solution;

<Step 3>

contacting the molding to a basic polymer solution, and thereafter,washing and removing the excessive basic polymer solution; and

<Step 4>

contacting the molding to an acidic polymer solution of amulti-component copolymer containing three or more components, andthereafter, washing and removing the excessive acidic polymer solution.

The medical device of the present invention has excellent lubricity andwettability, and therefore, the phenomenon that an ophthalmic lensadheres to a cornea at the time of wearing the ophthalmic lens, which isconsidered as a problem of a conventional low water content softophthalmic lens, can be significantly reduced or avoided. In addition,in the medical device of an embodiment of the present invention, a layermade of an acidic polymer and a basic polymer is provided by treatingthe medical device with a solution of at least a kind of multi-componentcopolymer of three or more components, and therefore, the risk ofbacterial proliferation can be reduced by improving an antifoulingproperty to a body liquid such as a lacrimal fluid. In addition,according to a preferable aspect of the present invention, a medicaldevice having high oxygen permeability, excellent wettability, excellentwearing feeling by being flexible, and excellent mechanical propertiessuch as folding resistance can be provided. The medical device of thepresent invention also has an advantage that the medical device can beproduced inexpensively in a simple process.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram illustrating an apparatus for measuring asurface friction coefficient of samples of a medical device according toan embodiment of the present invention.

FIG. 2 is a schematic diagram illustrating constitution of a main partof a measuring jig and a friction element in the surface frictioncoefficient measurement apparatus illustrated in FIG. 1.

FIG. 3 is a partial sectional view illustrating constitution of the mainpart of the measuring jig and the friction element in the surfacefriction coefficient measurement apparatus illustrated in FIG. 1.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

A medical device used in the present invention means a device that isused for medical use and is used by being in contact with a patient orbeing in contact with a tissue taken from a patient such as blood orother body fluids. Preferably, ophthalmic lenses, endoscopes, catheters,infusion tubes, gas transport tubes, stents, sheaths, cuffs, tubeconnectors, access ports, drainage bags, blood circuits, skin materials,or drug carriers can be exemplified.

In the base material used in the medical device of the presentinvention, a low water content base material means a base materialhaving a water content of 10% by mass or less, and a water-containingbase material means a base material having a water content of more than10% by mass.

Here, the water content is determined by, for example, {(Mass in wetstate)−(Mass in dry state)/Mass in wet state} from a mass in a dry stateof a test specimen having a film shape and a mass after wiping off thesurface water of the test specimen in a wet state by a borate buffersolution.

In the case of the low water content base material, particularly in thecase of use as an ophthalmic lens, the water content of the medicaldevice of the present invention is preferably 10% by mass or less, morepreferably 5% by mass or less, and further preferably less than 1% bymass.

In the case of the water-containing base material, particularly in thecase of use as an ophthalmic lens, the water content of the medicaldevice of the present invention is preferably 12 to 80% by mass, morepreferably 20 to 60% by mass, and further preferably 30 to 50% by mass.

In a copolymer used for the layer made of an acidic polymer and a basicpolymer of the medical device of the present invention, a copolymer of“n components” represents a copolymer obtained by copolymerizing n kindsof monomers. Here, as a mass of a copolymer is determined to be astandard (100% by mass), a monomer having a content of less than 0.1% bymass in the case of the acidic monomer and the basic monomer and lessthan 1% by mass in the case of another monomer are not counted as a kindof monomer. In addition, a multi-component copolymer means a copolymerof three or more components, that is, a copolymer obtained bycopolymerizing three or more kinds of monomers.

A multi-component copolymer used in the medical device of the presentinvention is a copolymer made of preferably 10 components or less, morepreferably 7 components or less, further preferably 5 components orless, and most preferably 3 components because, when kinds ofcopolymerization monomers are too many, a copolymerization ratios ofeach monomer are relatively too low, and therefore, expected physicalproperties cannot be provided. The multi-component copolymer may be arandom copolymer or a block copolymer, and may be a copolymer in whichonly a part of the components is a block copolymer and the othercomponents are a random copolymer.

A tensile modulus of the medical device of the present invention ispreferably 0.01 to 5 MPa, more preferably 0.1 to 3 MPa, furtherpreferably 0.1 to 2 MPa, particularly preferably 0.1 to 1 MPa, and mostpreferably 0.1 to 0.6 MPa. When the tensile modulus is too small, themedical device tends to be difficult to handle because the medicaldevice is too soft. When the tensile modulus is too large, the medicaldevice tends to have bad wearing feeling because the medical device istoo stiff. When the tensile modulus is 2 MPa or less, excellent wearingfeeling is obtained and when 1 MPa or less, more excellent wearingfeeling is obtained, which is preferable. The tensile modulus ismeasured using a sample in a wet state.

A tensile elongation (elongation at break) of the medical device of thepresent invention is preferably 100% to 1000% and more preferably 200%to 700%. When the tensile elongation is small, the medical devicebecomes easy to break, which is not preferable. When the tensileelongation is too large, the medical device tends to be easy to deform,which is not preferable. The tensile elongation is measured using asample in a wet state.

It is important from the viewpoint of bioaffinity that the surface ofthe medical device of the present invention has excellent wettability,and therefore, a dynamic contact angle (at the time of advance,immersion rate: 0.1 mm/sec) is preferably 100° or less, more preferably90° or less, and further preferably 80° or less. From the viewpoint ofpreventing the medical device from sticking to a cornea of a wearer, thedynamic contact angle is preferably lower, and is preferably 65° orless, more preferably 60° or less, further preferably 55° or less,particularly preferably 50° or less, and most preferably 45° or less.The dynamic contact angle is measured to a borate buffer solution usinga sample in a wet state by the borate buffer solution.

It is also important from the viewpoint of bioaffinity that the surfaceof the medical device of the present invention has excellent wettabilityand the wettability is particularly important from the viewpoint ofpreventing from sticking to a cornea of a wearer when the medical deviceis used as an ophthalmic lens. From this viewpoint, liquid filmretention time of the surface of the medical device is preferablylonger. Here, the liquid film retention time is a time in which a liquidfilm on the surface of the medical device is not broken but retainedwhen the medical device immersed into a borate buffer solution is pulledout from the solution and retained so that the surface (a diameterdirection in the case of an ophthalmic lens) is set to a vertical statein the air. The liquid film retention time is preferably 5 seconds ormore, further preferably 10 seconds or more, and most preferably 20seconds or more. Here, the diameter is a diameter of a circleconstituted by an edge part of the lens. The liquid film retention timeis measured using a sample in a wet state by the borate buffer solution.

From the viewpoint of facilitating the movement when the medical deviceis in contact with a surface of a body tissue, and particularly from theviewpoint of preventing sticking to a cornea of a wearer in the case ofan ophthalmic lens, the surface of the medical device preferably hasexcellent lubricity. As in Examples in this specification, lubricity canbe evaluated by sensory evaluation when the medical device is rubbedfive times with human fingers. The evaluation of the lubricity of themedical device of the present invention is preferably C or higher, morepreferably B or higher, and most preferably A or higher. As an indicatorfor indicating the lubricity more objectively and quantitatively, it isalso possible to evaluate by using a surface friction coefficient ratioas measured by the following method. The surface friction coefficient ismeasured by using a contact lens-shaped sample or a film-shaped samplethat is cut out in a circular shape with a diameter of 14 mm. FrictionTester KES-SE (Kato Tech Co., Ltd.) is used to measure the surfacefriction coefficient. FIG. 1 is a schematic diagram illustrating anapparatus for measuring the surface friction coefficient of samples ofthe medical device according to the present invention. FIG. 2 is aschematic diagram illustrating the constitution of a main part of ameasuring jig and a friction element for measuring the surface frictioncoefficient of the sample of the medical device according to the presentinvention seen from a direction of an arrow A illustrated in FIG. 1.FIG. 3 is a partial sectional view illustrating the constitution of themain part of the measuring jig and the friction element for measuringthe surface friction coefficient of the sample of the medical deviceaccording to the present invention. First, a plate of “Teflon(registered trademark)” (manufactured by DuPont)(65 mm×100 mm×1.0 mm,not illustrated in FIG. 3) is horizontally placed on a sample stage 10of an apparatus 1, and then a quartz glass plate 10 a (55 mm×90 mm×1.0mm) having a smooth surface is horizontally placed on the sample stage10 and fixed. The plate of “Teflon (registered trademark)” (manufacturedby DuPont) and the quartz glass plate having sufficiently high flatnessare used. Here, the quartz glass plate 10 a has a state in which thesurface is wiped off with Kimwipe (registered trademark)” (manufacturedby Nippon Paper Crecia Ltd.) to be clean and dry for each measurement.In the measurement, the measurement is carried out by attaching threepieces of samples S to a friction element 20 of a measurement jig 11 (aweight of 62 g=W) illustrated in FIGS. 2 and 3. At this time, the sampleS are placed on an apex of a mounting holder 21 of the friction element20, and thereafter the sample S are held by a gasket 22 and fixed by anut 23. In a state that the samples S are projected from the apex of the20 friction element and fixed, each of 0.1 mL of the borate buffersolution in the case of the following condition A or physiologic salinein the case of the following condition B is dropped at each centralportion of the three samples. Thereafter, the measurement jig 11 israpidly attached to the apparatus 1. In a state that all three samples Sare in contact with the quartz glass plate 10 a, a stress (F) in ahorizontal direction when the sample stage 10 is moved in a horizontaldirection (an arrow Y) at a speed of 1.0 mm/second is detected by afriction detection part 12 and measured by a force measuring device 13.

The surface friction coefficient (MIU) is determined form the followingformula.MIU=F/W

A moving distance is set to 30 mm, and the measurement of MIU is carriedout in every 0.1 seconds.

The surface friction coefficient is determined to be an average value ofMIU in an interval (at least 5 mm) where MIU in a travel distance of 5mm to 25 mm is stabilized (a value obtained by dividing the sum of MIUat each time in the interval with the number of data of MIU).

At this time, a surface friction coefficient in the condition A isdefended as MIU_(a) and a surface friction coefficient in the conditionB is defended as MIU_(b).

Condition A: To carry out measurements using samples in the wet state bythe borate buffer solution.

Condition B: To carry out measurements using samples in the wet state bythe physiologic saline.

In FIG. 3, the thickness of a support plate for supporting the frictionelement 20 the measurement jig 11 is defined as d1. In the frictionelement 20, when a projection length from the measurement jig 11 isdefined as d2, a diameter of a portion in contact with the lens in themounting holder 21 being defined as d3, and a diameter of the outerperiphery of the nut 23 being defined as d4, d1 is 1.5 (mm); d2 is 22.4(mm); d3 is 14 (mm), and d4 is 18 (mm).

A surface friction coefficient in the condition A (MIU_(o)) of “Acuvue(registered trademark) Oasys” (Johnson & Johnson, Inc.) in the methoddescribed above is determined. Surface friction coefficient ratios Q_(a)and Q_(b) are determined by the following formula.Q _(a) =MIU _(a) /MIU _(o)Q _(b) =MIU _(b) /MIU _(o)

A smaller surface friction coefficient ratio (Q_(b) and Q_(a)) describedlater that is measured by the method described above is preferable.

Furthermore, in the friction described above, the surface frictioncoefficient ratio (Q_(a)) of the medical device of the present inventionat the time of wetting with the borate buffer solution is preferably 2or less, more preferably 1.6 or lower, and further preferably 1 or less.It should be noted that:Q _(a) =MIU _(a) /MIU _(o)

where MIU_(a) represents the surface friction coefficient between themedical device and the smooth quartz glass plate in the wet state by theborate buffer solution. MIU_(o) represents a surface frictioncoefficient between “Acuvue (registered trademark) Oasys” and the smoothquartz glass plate in the wet state by the borate buffer solution.

The smaller the surface friction coefficient ratio Q_(a), the smallerthe surface friction and the smaller the influence on a living body whenrubbing is caused between the medical device and the living body (forexample, cornea or palpebral conjunctiva in the case of a contact lens),which is preferable. In this sense, the surface friction coefficientratio Q_(a) is preferably 1 or less, more preferably 0.8 or less, andmost preferably 0.6 or less.

In addition, the surface friction coefficient ratio Q_(b) at the time ofwetting by the physiologic saline is preferably 3 or less, morepreferably 2 or less, and further preferably 1.5 or less. It should benoted that:Q _(b) =MIU _(b) /MIU _(o)

where MIU_(b) represents the surface friction coefficient between themedical device and the smooth quartz glass plate in the wet state by thephysiologic saline.

In the medical device in which a layer made by an acidic polymer and abasic polymer is formed on at least a part of a base material, which isone of the preferable aspects of the present invention, it has beenfound that Q_(b) tends to be larger than Q_(a) and Q_(b) issignificantly large in some cases. The physiologic saline, however, is asimilar liquid to body fluids (for example, lacrimal fluid in the caseof a contact lens), and, from the viewpoint of preventing sticking ofthe medical device to a surface of a living body (a cornea in the caseof an ophthalmic lens), it is preferable that the surface frictioncoefficient ratio (Q_(b)) at the time of wetting by the physiologicsaline is also small.

The smaller the surface friction coefficient ratio Q_(b), the smallerthe surface friction and the smaller the influence on a living body whenrubbing is caused between the medical device and the living body (forexample, cornea or palpebral conjunctiva in the case of a contact lens),which is preferable. In this sense, the surface friction coefficientratio Q_(b) is preferably 1.5 or less, more preferably 1.0 or less, andmost preferably 0.8 or less.

Furthermore, in the medical device of the present invention, differencebetween the surface friction coefficient ratio Q_(b) at the time ofwetting by the borate buffer solution and the surface frictioncoefficient ratio Q_(a) at the time of wetting by the physiologic saline(Q_(b)-Q_(a)) is preferably 1.6 or less, more preferably 1.3 or less,and further preferably 1.0 or less. When the difference between thesurface friction coefficient ratio Q_(a) and the surface frictioncoefficient ratio Q_(b) is small, difference between lubricity at thetime of applying the medical device to a living body to lubricity at thetime before application (for example, at the time of opening package)tends to be small, which is preferable.

Antifouling properties of the medical device of the present inventioncan be evaluated by mucin adhesion, lipid (methyl palmitate) adhesion,and an immersion test into artificial lacrimal fluid. The smaller theadhesion amount measured by these evaluations, the more excellent thewearing feeling and the less the risk of bacterial proliferation, whichis preferable. An adhesion amount of mucin when a low water content basematerial is used is preferably 5 μg/cm² or less, more preferably 4μg/cm² or less, and most preferably 3 μg/cm² or less.

From the viewpoint of oxygen supply from the atmosphere to a body tissueof a patient (an eye in the case of ophthalmic lens), the medical deviceof the present invention preferably has high oxygen permeability. Anoxygen permeability coefficient [×10⁻¹¹ (cm²/sec)·mLO₂/(mL·hPa)] ispreferably 30 to 2000, more preferably 45 to 1500, further preferably 65to 1000, and most preferably 75 to 700. When the oxygen permeabilitycoefficient is set to too large, other properties such as mechanicalproperties may be adversely affected, which is not preferable. Theoxygen permeability is measured using a sample in a dry state.

Depending on used application, the medical device of an embodiment ofthe present invention includes formed bodies having a lens shape or asheet-like shape (hereinafter, referred to as a base material), and alayer made of an acidic polymer and a basic polymer is formed on atleast a part of the surface of the base material.

In order to have high oxygen permeability and in order to obtain strongadhesion not though covalent bonds between the base material and apolymer coated to the surface, the base material preferably contains 5%by mass or more of silicon atoms. A content of the silicon atoms (% bymass) is calculated based on a mass of the base material in a dry stateas a standard (100% by mass). A content of the silicon atoms in the basematerial is preferably 5% by mass to 36% by mass, more preferably 7% bymass to 30% by mass, further preferably 10% by mass to 30% by mass, andmost preferably 12% by mass to 26% by mass. When the content of thesilicon atoms is too large, the tensile modulus may be high, which isnot preferable.

A content of the silicon atoms in the base material can be measured bythe following method. A sufficiently dried base material is weighed andcharged into a platinum crucible, and sulfuric acid is added and themixture is heated with a hot plate and a burner to form ash. The ash ismelted with sodium carbonate and water is added to the mixture todissolve with heat. Thereafter, nitric acid is added and a solutionhaving a constant volume is made with water. For this solution, siliconatoms are measured by ICP emission spectroscopy, and a content in thebase material is determined.

When the medical device of the present invention is used as anophthalmic lens, high transparency is preferable because the ophthalmiclens is an optical product. As a criterion of the transparency, it ispreferable that the lens is clear and has no turbidity when the lens isvisually observed. Moreover, when an ophthalmic lens is observed with alens projector, it is preferable that turbidity is hardly observed or isnot observed at all and it is the most preferable that turbidity is notobserved at all.

When an application of the medical device is an ophthalmic lens, a totallight transmittance of the medical device of the present invention ispreferably 85% or more, more preferably 88% or more, and most preferably91% or more in a wet state of the ophthalmic lens in terms of quality.

As one aspect, preferably, a base material of the medical deviceaccording to the present invention includes a polymer of a component Athat has a plurality of polymerizable functional groups per molecule andis a polysiloxane compound having a number average molecular weight of6000 or more or a copolymer of the component A and other compound havinga polymerizable functional group other than the component A as a maincomponent. Here, the main component means a component that is includedin 50% by mass or more when a mass of the base material in a dry stateis determined to be a standard (100% by mass).

In this specification, a polysiloxane compound is a compound having aSi—O—Si—O—Si bond. The Si—O—Si—O—Si bond is made of continuous Si—O—Sibonds (a siloxanyl group).

A number average molecular weight of the component A is preferably 6000or more. The inventors of the present invention have found that, whenthe number average molecular weight of the component A is in this range,the medical device having flexibility, excellent wearing feeling, andexcellent mechanical properties such as folding resistance can beobtained. The number average molecular weight of the polysiloxanecompound of the component A is preferably 8000 or more because the basematerial having excellent mechanical properties such as foldingresistance can be obtained. The number average molecular weight of thecomponent A is preferably in a range of 8000 to 100000, more preferablyin a range of 9000 to 70000, and further preferably in a range of 10000to 50000. When the number average molecular weight of the component A istoo small, mechanical properties such as folding resistance tends todeteriorate, and particularly when the number average molecular weightis less than 6000, the folding resistance deteriorates. When the numberaverage molecular weight of the component A is too large, flexibilityand transparency tend to deteriorate, which is not preferable.

A dispersity of the component A (a value calculated by dividing a massaverage molecular weight by a number average molecular weight) ispreferably 6 or less, more preferably 3 or less, further preferably 2 orless, and most preferably 1.5 or less. When the dispersity of thecomponent A is small, advantages that transparency of the obtainedmedical device is improved because compatibility with other componentsis improved; extractable components included in the obtained medicaldevice is reduced; and a shrinkage ratio associated with medical devicemolding is reduced are generated. When the medical device is used as anophthalmic lens, the shrinkage ratio associated with lens molding isevaluated by a lens molding ratio=[Lens diameter]/[Diameter of moldcavity]. As the lens molding ratio is closer to 1, it is easier toproduce a high quality lens stably. The molding ratio is preferably in arange of 0.85 to 2.0, more preferably in a range of 0.9 to 1.5, and mostpreferably in a range of 0.91 to 1.3.

In the present invention, the number average molecular weight of thecomponent A is an number average molecular weight in terms ofpolystyrene measured by a gel permeation chromatography method (a GPCmethod) using chloroform as a solvent. The mass average molecular weightand the dispersity (the value calculated by dividing a mass averagemolecular weight by a number average molecular weight) are measured in asimilar method.

Here, in this specification, the mass average molecular weight may berepresented by Mw and the number average molecular weight may berepresented by Mn. In addition, a molecular weight of 1000 may berepresented as 1 kD. For example, a “Mw of 33 kD” represents a “massaverage molecular weight of 33000”.

The component A is a polysiloxane compound having a plurality ofpolymerizable functional groups. The number of the polymerizablefunctional group of the component A may be two or more per molecule,and, from the viewpoint that a more flexible (low modulus) base materialis easily obtained, the number is preferably two per molecule. Thecomponent A may have the polymerizable functional groups in any positionin a molecular chain, and preferably has a structure in which both endsof the molecular chain have polymerizable functional groups.

The polymerizable functional group of the component A is preferably aradical polymerizable functional group and more preferably a functionalgroup having a carbon-carbon double bond. Examples of the preferablepolymerizable functional group include a vinyl group, an allyl group, a(meth)acryloyl group, an α-alkoxymethylacryloyl group, a maleic acidresidue, a fumaric acid residue, an itaconic acid residue, a crotonicacid residues, an isocrotonic acid residue, and a citraconic acidresidue. Among them, the (meth)acryloyl group is the most preferablefunctional group because the (meth)acryloyl group is highlypolymerizable. When the component A has two or more polymerizablefunctional group in a molecule, polymerizable functional groups in amolecule may be the same as or different from each other.

Here, in this specification, the term “(meth)acryloyl” represents bothof methacryloyl and acryloyl, and the terms “(meth)acrylic acid” and“(meth)acrylate” have similar meaning.

As the component A, a component having the following formula (A1) ispreferable.

In formula (A1), X¹ and X² each independently represents a polymerizablefunctional group. R¹ to R⁸ each independently represents a substituentselected from hydrogen, an alkyl group having a carbon number of 1 to20, a phenyl group, and a fluoroalkyl group having a carbon number of 1to 20. L¹ and L² each independently represents a divalent group. a and beach independently represents an integer of 0 to 1500. Here, a and b arenot zero at the same time.

X¹ and X² are preferably radical polymerizable functional groups andmore preferably functional groups having a carbon-carbon double bond.Examples of the preferable polymerizable functional group include avinyl group, an allyl group, a (meth)acryloyl group, anα-alkoxymethylacryloyl group, a maleic acid residue, a fumaric acidresidue, an itaconic acid residue, a crotonic acid residues, anisocrotonic acid residue, and a citraconic acid residue. Among them, the(meth)acryloyl group is the most preferable functional group because the(meth)acryloyl group is highly polymerizable.

Specific preferable examples of R¹ to R⁸ include hydrogen; an alkylgroup having a carbon number of 1 to 20 such as a methyl group, an ethylgroup, a propyl group, an isopropyl group, a butyl group, a t-butylgroup, a decyl group, a dodecyl group, and an octadecyl group; a phenylgroup, and a fluoroalkyl group having a carbon number of 1 to 20 such asa trifluoromethyl group, a trifluoroethyl group, a trifluoropropylgroup, a tetrafluoropropyl group, a hexafluoroisopropyl group, apentafluorobutyl group, a heptafluoropentyl group, a nonafluorohexylgroup, a hexafluorobutyl group, a heptafluorobutyl group, anoctafluoropentyl group, a nonafluoropentyl group, a dodecafluoroheptylgroup, a tridecafluoroheptyl group, a dodecafluorooctyl group, atridecafluorooctyl group, a hexadecafluorodecyl group, aheptadecafluorodecyl group, a pentafluoropropyl group, atetradecafluorooctyl group, a pentadecafluorooctyl group, anoctadecafluorodecyl group, and a nonadecafluorodecyl group. Among them,from the viewpoint of providing excellent mechanical properties and highoxygen permeability to the medical device, more preferable is hydrogenand a methyl group, and the most preferable is a methyl group.

As L¹ and L², a divalent group having a carbon number of 1 to 20 ispreferable. Among them, groups represented by the following formulae(LE1) to (LE12) are preferable; among them, the groups represented bythe following formulae (LE1), (LE3), (LE9), and (LE11) are morepreferable; the groups represented by the following formulae (LE1) and(LE3) are further preferable; and the group represented by the followingformula (LE1) is the most preferable, because these groups have anadvantage that the compound of formula (A1) is easily obtained in highpurity. Here, the following formulae (LE1) to (LE12) are illustrated asan end bonding to the polymerizable functional group X¹ or X² is in theleft side and an end bonding to silicon atom is in the right side.OCH₂CH₂CH₂  (LE1)NHCH₂CH₂CH₂  (LE2)OCH₂CH₂NHCOOCH₂CH₂CH₂  (LE3)OCH₂CH₂NHCONHCH₂CH₂CH₂  (LE4)OCH₂CH₂CH₂CH₂  (LE5)NHCH₂CH₂CH₂CH₂  (LE6)OCH₂CH₂NHCOOCH₂CH₂CH₂CH₂  (LE7)OCH₂CH₂NHCONHCH₂CH₂CH₂CH₂  (LE8)OCH₂CH₂OCH₂CH₂CH₂  (LE9)NHCH₂CH₂OCH₂CH₂CH₂  (LE10)OCH₂CH₂NHCOOCH₂CH₂OCH₂CH₂CH₂  (LE11)OCH₂CH₂NHCONHCH₂CH₂OCH₂CH₂CH₂  (LE12)

In addition, in formula (A1), a and b each independently represents aninteger of 0 to 1500. Here, a and b are not zero at the same time.(a+b), which is a total value of a and b, is preferably 80 or more, morepreferably 100 or more, more preferably 100 to 1400, more preferably 120to 950, and further preferably 130 to 700.

In formula (A1), when all of R¹ to R⁸ are methyl groups, b equals to 0,and a is preferably 80 to 1500, more preferably 100 to 1400, morepreferably 120 to 950, and further preferably 130 to 700. In this case,the value of a is determined by a molecular weight of the polysiloxanecompound of the component A.

In the base material of the medical device of the present invention, thecomponent A may be used singly or may be used in combination of two ormore.

In the base material of the medical device of the present invention, asother compound copolymerized with the component A, a component B being apolymerizable monomer having a fluoroalkyl group is preferable. Thecomponent B has water repellent and oil repellent properties due toreduction in critical surface tension caused by the fluoroalkyl group,and thereby, the effect that reduces contamination of the medical devicesurface caused by components such as protein and lipid in a body fluidis generated. In addition, the component B has the effect that providesa medical device having flexibility, excellent wearing feeling, andexcellent mechanical properties such as folding resistance. Specificpreferable examples of the fluoroalkyl group of the component B includefluoroalkyl groups having a carbon number of 1 to 20 such as atrifluoromethyl group, a trifluoroethyl group, a trifluoropropyl group,a tetrafluoropropyl group, a hexafluoroisopropyl group, apentafluorobutyl group, a heptafluoropentyl group, a nonafluorohexylgroup, a hexafluorobutyl group, a heptafluorobutyl group, anoctafluoropentyl group, a nonafluoropentyl group, a dodecafluoroheptylgroup, a tridecafluoroheptyl group, a dodecafluorooctyl group, atridecafluorooctyl group, a hexadecafluorodecyl group, aheptadecafluorodecyl group, a pentafluoropropyl group, atetradecafluorooctyl group, a pentadecafluorooctyl group, anoctadecafluorodecyl group, and a nonadecafluorodecyl group. The examplesmore preferably include fluoroalkyl groups having a carbon number of 2to 8 such as a trifluoroethyl group, a tetrafluoropropyl group, ahexafluoroisopropyl group, an octafluoropentyl group, and adodecafluorooctyl group, and most preferably is a trifluoroethyl group

A polymerizable functional groups of the component B is preferably aradical polymerizable functional group and more preferably a functionalgroup having a carbon-carbon double bond. Examples of the preferablepolymerizable functional group include a vinyl group, an allyl group, a(meth)acryloyl group, an α-alkoxymethylacryloyl group, a maleic acidresidue, a fumaric acid residue, an itaconic acid residue, a crotonicacid residues, an isocrotonic acid residue, and a citraconic acidresidue. Among them, the (meth)acryloyl group is the most preferablefunctional group because the (meth)acryloyl group is highlypolymerizable.

A (meth)acrylic acid fluoroalkyl ester is the most preferable as thecomponent B because this ester has significant effect that provides themedical device having flexibility, excellent wearing feeling, andexcellent mechanical properties such as folding resistance. Specificexamples of this (meth)acrylic acid fluoroalkyl ester includetrifluoroethyl(meth)acrylate, tetrafluoroethyl(meth)acrylate,trifluoropropyl(meth)acrylate, tetrafluoropropyl(meth)acrylate,pentafluoropropyl(meth)acrylate, hexafluorobutyl(meth)acrylate,hexafluoroisopropyl(meth)acrylate, heptafluorobutyl(meth)acrylate,octafluoropentyl(meth)acrylate, nonafluoropentyl(meth)acrylate,dodecafluoropentyl(meth)acrylate, dodecafluoroheptyl(meth)acrylate,dodecafluorooctyl(meth)acrylate, and tridecafluoroheptyl(meth)acrylate.Trifluoroethyl(meth)acrylate, tetrafluoroethyl(meth)acrylate,hexafluoroisopropyl(meth)acrylate, octafluoropentyl(meth)acrylate, anddodecafluorooctyl(meth)acrylate are preferably used. The most preferableis trifluoroethyl(meth)acrylate.

In the base material of the medical device of the present invention, thecomponent B may be used singly or may be used in combination of two ormore.

A content of the component B in the copolymer to 100 parts by mass ofthe component A is preferably 10 to 500 parts by mass, more preferably20 to 400 parts by mass, and further preferably 20 to 200 parts by mass.When the used amount of the component B is too small, the base materialtends to generate white turbidity and have insufficient mechanicalproperties such as folding resistance.

In addition, as a copolymer used in the base material, a copolymer inwhich a component different from the component A and the component B(hereinafter referred to as a component C) is further copolymerized inaddition to the component A and the component B may be used.

As the component C, a component that lowers a glass transition point ofthe copolymer to room temperature or to a temperature of 0° C. or lessis preferable. Such a component decreases cohesive energy, andtherefore, have effect to provide the copolymer with rubber elasticityand softness.

A polymerizable functional groups in the component C is preferably aradical polymerizable functional group and more preferably a functionalgroup having a carbon-carbon double bond. Examples of the preferablepolymerizable functional group include a vinyl group, an allyl group, a(meth)acryloyl group, an α-alkoxymethylacryloyl group, a maleic acidresidue, a fumaric acid residue, an itaconic acid residue, a crotonicacid residues, an isocrotonic acid residue, and a citraconic acidresidue. Among them, the (meth)acryloyl group is the most preferablefunctional group because the (meth)acryloyl group is highlypolymerizable.

As the component C, preferable examples for improving flexibility andmechanical properties such as folding resistance include (meth)acrylicacid alkyl esters, preferably (meth)acrylic acid alkyl esters in which acarbon number of the alkyl group is 1 to 20. Specific examples thereofcan include methyl(meth)acrylate, ethyl(meth)acrylate,n-propyl(meth)acrylate, n-butyl(meth)acrylate, tert-butyl(meth)acrylate,isobutyl(meth)acrylate, n-hexyl(meth)acrylate, n-octyl(meth)acrylate,2-ethylhexyl(meth)acrylate, n-heptyl(meth)acrylate,n-nonyl(meth)acrylate, n-decyl(meth)acrylate, isodecyl(meth)acrylate,n-lauryl(meth)acrylate, tridecyl(meth)acrylate, n-dodecyl(meth)acrylate,cyclopentyl(meth)acrylate, cyclohexyl(meth)acrylate, andn-stearyl(meth)acrylate, and more preferably includen-butyl(meth)acrylate, n-octyl(meth)acrylate, n-lauryl(meth)acrylate,and n-stearyl(meth)acrylate. Among them, (meth)acrylic acid alkyl estersin which a carbon number of the alkyl group is 1 to 10 are morepreferable. When the carbon number of the alkyl group is too large,transparency of the obtained medical device may be deteriorated, whichis not preferable.

In addition, in the base material of the medical device of the presentinvention, in order to improve mechanical properties, surfacewettability, and dimensional stability of the medical device, a monomer(the component C) other than the component A and the component Bdescribed below can be copolymerized in accordance with request.

As the monomer (the component C) for improving mechanical properties,for example, aromatic vinyl compound such as styrene, tert-butylstyrene,and α-methyl styrene are included.

As the monomer (the component C) for improving surface wettability, forexample, methacrylic acid, acrylic acid, itaconic acid, 2-hydroxyethylmethacrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate,2-hydroxypropyl acrylate, glycerol methacrylate, polyethylene glycolmethacrylate, N,N-dimethyl acrylamide, N-methyl acrylamide,N,N-dimethylaminoethyl methacrylate, methylene-bis-acrylamide, diacetoneacrylamide, N-vinylpyrrolidone, N-vinylcaprolactam, N-vinylacetamide,and N-vinyl-N-methylacetamide are included. Among them, the monomerhaving an amino group or an amide group such as N,N-dimethyl acrylamide,N-methyl acrylamide, N,N-dimethylaminoethyl methacrylate,methylene-bis-acrylamide, diacetone acrylamide, N-vinylpyrrolidone,N-vinylcaprolactam, N-vinylacetamide, and N-vinyl-N-methylacetamide arepreferable. Particularly, the monomer having an amino group such asN,N-dimethylaminoethyl methacrylate is preferable from the viewpoint ofexcellent compatibility with a dye.

As the monomer (the component C) for improving dimensional stability ofthe medical device, for example, ethylene glycol dimethacrylate,diethylene glycol dimethacrylate, triethylene glycol dimethacrylate,polyethylene glycol dimethacrylate, trimethylolpropane trimethacrylate,pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinylmethacrylate, acrylic and methacrylate, and acrylates corresponding tothese methacrylate, divinyl benzene, and triallyl isocyanurate areincluded.

In the base material of the medical device of the present invention, thecomponent C may be used singly or in combination of two or more.

A used amount of the component C to 100 parts by mass of the component Ais preferably 0.001 to 400 parts by mass, more preferably 0.01 to 300parts by mass, further preferably 0.01 to 200 parts by mass, and mostpreferably 0.01 to 30 parts by mass. When the used amount of thecomponent C is too small, effects which are expected to the component Ctend not to be obtained. When the used amount of the component C is toolarge, the medical device tends to generate white turbidity and haveinsufficient mechanical properties such as folding resistance.

The medical device of the present invention may further include othercomponents (components Ck) such as an ultraviolet absorber, a dye, acolorant, a wetting agent, a slip agent, pharmaceutical andnutraceutical components, a compatibilizing component, an antimicrobialcomponent, and a release agent. Any of the components described abovemay be included in the form of a non-reactive component or in the formof a copolymer component. When one or more of the components Ck areused, each of a total used amounts of the components Ck to 100 parts bymass to the composition A is preferably 0.00001 to 100 parts by mass,more preferably 0.0001 to 30 parts by mass, and further preferably 0.001to 5 parts by mass. When the used amount of the component Ck is toosmall, expected effects of the component Ck such as ultravioletabsorption and coloring tend not to be sufficiently obtained. When theused amount of the component Ck is too large, the obtained medicaldevice tends to generate white turbidity, which is not preferable.

When the base material of the medical device (particularly, anophthalmic lens) of the present invention contains an ultravioletabsorber, body tissues of a wearer (an eye in the case of an ophthalmiclens) can be protected from harmful ultraviolet. In addition, when themedical device contains a colorant, the medical device is colored andeasily distinguished, and therefore, convenience at the time of handlingis improved.

Any of the components described above may be included in the form of anon-reactive component or in the form of a copolymer component. When thecomponent described above is copolymerized, that is, when an ultravioletabsorber having a polymerizable functional group, a colorant having apolymerizable functional group, or the like is used, possibility ofelution is reduced since the component is copolymerized to the basematerial and immobilized, which is preferable.

As an aspect, the base material of the medical device according to thepresent invention is preferably made of the component (the component Ck)selected from the ultraviolet absorber and the colorant, two or morekinds of the component C, and the component A and the component B. Inthis case, as the components C, at least a kind of (meth)acrylic acidalkyl ester having a carbon number of 1 to 10 and at least a kind of amonomer for improving the surface wettability are preferably selected.By using two or more kinds of the components C, affinity of theultraviolet absorber and colorant is improved and a transparent basematerial can be easily obtained.

When the ultraviolet absorber is used, a used amount thereof to 100parts by mass of the component A is preferably 0.01 to 20 parts by mass,more preferably 0.05 to 10 parts by mass, and further preferably 0.1 to2 parts by mass. When the colorant is used, a used amount thereof to 100parts by mass of the component A is preferably 0.00001 to 5 parts bymass, more preferably 0.0001 to 1 parts by mass, and further preferably0.0001 to 0.5 parts by mass. When the content of the ultravioletabsorber or the colorant is too small, effect of the ultravioletabsorber or effect of the colorant is difficult to obtain. On thecontrary, when the content thereof is too large, it is difficult to makethese components dissolve in the base material.

Furthermore, as a copolymer used for the base material, a copolymer inwhich a component M is further copolymerized in addition to thecomponent A may be used. The component M is a “monofunctional monomerhaving a polymerizable functional group and a siloxanyl group in onemolecule”.

In this specification, the siloxanyl group means a group having aSi—O—Si bond.

The siloxanyl group of the component M is preferably a straight-chain.When the siloxanyl group is a straight-chain, a shape recovery propertyof the obtained medical device is improved. Here, the straight-chainindicates a structure represented by Si—(O—Si)_(n-1)—O—Si whose startpoint is a silicon atom bonded to a group having a polymerizable groupand that is sequentially bonded in the form of a line (here, nrepresents an integer of 2 or more). In order to obtain a sufficientshape recovery property of the obtained medical device, n is preferablyan integer of 3 or more, more preferably 4 or more, further preferably 5or more, and most preferably 6 or more. In addition, “a siloxanyl groupbeing a straight-chain” means that the siloxanyl group has thestraight-chain structure and does not have Si—O—Si bonds which do notsatisfy the conditions of the straight-chain structure.

A number average molecular weight of the component M is preferably 300to 120000. When the number average molecular weight of the component Mis in this range, a base material having flexibility (low modulus),excellent wearing feeling, and excellent mechanical properties such asfolding resistance is obtained. The number average molecular weight ofthe component M is preferably 500 or more because the base materialhaving mechanical properties such as folding resistance and the shaperecovery property is obtained. The number average molecular weight ofthe component M is more preferably in a range of 1000 to 25000 andfurther preferably in a range of 5000 to 15000. When the number averagemolecular weight of the component M is too small, mechanical propertiessuch as folding resistance and the shape recovery property tend todeteriorate, and particularly when the number average molecular weightis less than 500, the folding resistance and the shape recovery propertymay deteriorate. When the number average molecular weight of thecomponent M is too large, flexibility and transparency tend todeteriorate, which is not preferable.

A polymerizable functional groups in the component M is preferably aradical polymerizable functional group and more preferably a functionalgroup having a carbon-carbon double bond. Examples of the preferablepolymerizable functional group include a vinyl group, an allyl group, a(meth)acryloyl group, an α-alkoxymethylacryloyl group, a maleic acidresidue, a fumaric acid residue, an itaconic acid residue, a crotonicacid residues, an isocrotonic acid residue, and a citraconic acidresidue. Among them, the (meth)acryloyl group is the most preferablefunctional group because the (meth)acryloyl group is highlypolymerizable.

As the component M, a component having a structure of the followingformula (ML1) is preferable.

In formula (ML1), X³ represents a polymerizable functional group. R⁹ toR¹⁷ each independently represents a substituent selected from hydrogen,an alkyl group having a carbon number of 1 to 20, a phenyl group, and afluoroalkyl group having a carbon number of 1 to 20. L³ represents adivalent group. c and d each independently represents an integer of 0 to700. Here, c and d are not zero at the same time.

X³ is preferably a radical polymerizable functional group and morepreferably a functional group having a carbon-carbon double bond.Examples of the preferable polymerizable functional group include avinyl group, an allyl group, a (meth)acryloyl group, anα-alkoxymethylacryloyl group, a maleic acid residue, a fumaric acidresidue, an itaconic acid residue, a crotonic acid residues, anisocrotonic acid residue, and a citraconic acid residue. Among them, the(meth)acryloyl group is the most preferable functional group because the(meth)acryloyl group is highly polymerizable.

In addition, the polymerizable functional group of the component M ispreferably copolymerizable with the polymerizable functional group ofthe component A because a medical device having excellent mechanicalproperties is easily obtained, and is more preferably the same as thepolymerizable functional group of the component A because a medicaldevice having excellent surface characteristics is easily obtained byuniformly copolymerizing the component M and the component A.

Specific preferable examples of R⁹ to R¹⁷ include hydrogen; an alkylgroup having a carbon number of 1 to 20 such as a methyl group, an ethylgroup, a propyl group, an isopropyl group, a butyl group, a t-butylgroup, a decyl group, a dodecyl group, and an octadecyl group; a phenylgroup, and a fluoroalkyl group having a carbon number of 1 to 20 such asa trifluoromethyl group, a trifluoroethyl group, a trifluoropropylgroup, a tetrafluoropropyl group, a hexafluoroisopropyl group, apentafluorobutyl group, a heptafluoropentyl group, a nonafluorohexylgroup, a hexafluorobutyl group, a heptafluorobutyl group, anoctafluoropentyl group, a nonafluoropentyl group, a dodecafluoroheptylgroup, a tridecafluoroheptyl group, a dodecafluorooctyl group, atridecafluorooctyl group, a hexadecafluorodecyl group, aheptadecafluorodecyl group, a tetrafluoropropyl group, apentafluoropropyl group, a tetradecafluorooctyl group, apentadecafluorooctyl group, an octadecafluorodecyl group, and anonadecafluorodecyl group. Among them, from the viewpoint of providingexcellent mechanical properties and high oxygen permeability to themedical device, more preferable is hydrogen and the methyl group, andmost preferable is the methyl group.

As L³, a divalent group having a carbon number of 1 to 20 is preferable.Among them, groups represented by the following formulae (LE1) to (LE12)are preferable; among them, the groups represented by the followingformulae (LE1), (LE3), (LE9) and (LE11) are more preferable; the groupsrepresented by the following formulae (LE1) and (LE3) are furtherpreferable; and the group represented by the following formula (LE1) isthe most preferable, because these groups have an advantage that thecompound of formula (ML1) is easily obtained in high purity. Here, thefollowing formulae (LE1) to (LE12) are illustrated as an end bonding tothe polymerizable functional group X³ is in the left side and an endbonding to silicon atom is in the right side.OCH₂CH₂CH₂  (LE1)NHCH₂CH₂CH₂  (LE2)OCH₂CH₂NHCOOCH₂CH₂CH₂  (LE3)OCH₂CH₂NHCONHCH₂CH₂CH₂  (LE4)OCH₂CH₂CH₂CH₂  (LE5)NHCH₂CH₂CH₂CH₂  (LE6)OCH₂CH₂NHCOOCH₂CH₂CH₂CH₂  (LE7)OCH₂CH₂NHCONHCH₂CH₂CH₂CH₂  (LE8)OCH₂CH₂OCH₂CH₂CH₂  (LE9)NHCH₂CH₂OCH₂CH₂CH₂  (LE10)OCH₂CH₂NHCOOCH₂CH₂OCH₂CH₂CH₂  (LE11)OCH₂CH₂NHCONHCH₂CH₂OCH₂CH₂CH₂  (LE12)

In formula (ML1), c and d each independently represents an integer of 0to 700. Here, c and d are not zero at the same time. (c+d), which is atotal value of c and d, is preferably 3 or more, more preferably 10 ormore, more preferably 10 to 500, more preferably 30 to 300, and furtherpreferably 50 to 200.

When all of R⁹ to R¹⁷ are methyl groups, d equals to 0, and a ispreferably 3 to 700, more preferably 10 to 500, more preferably 30 to300, and further preferably 50 to 200. In this case, the value of c isdetermined by a molecular weight of the component M.

In the base material of the medical device of the present invention, thecomponent M may be used singly or may be used in combination of two ormore.

The base material of the medical device of the present inventioncontains an adequate amount of the component M, and thereby, crosslinkdensity is decreased and a degree of freedom of the polymer isincreased, and therefore, an adequately soft and low modulus basematerial can be realized. On the contrary, when the content of thecomponent M is too small, the crosslink density becomes high and thebase material becomes stiff. In addition, when the content of thecomponent M is too large, the base material becomes too soft and easilybreak, which is not preferable.

In the base material of the medical device of the present invention, asa mass ratio of the component M and the component A, the component M ispreferably 5 to 200 parts by mass, more preferably 7 to 150 parts bymass, and most preferably 10 to 100 parts by mass to the 100 parts ofthe component A. When the content of the component M to 100 parts bymass of the component A is less than 5 parts by mass, the crosslinkdensity becomes high and the base material becomes stiff. In addition,when the content of the component M to 100 parts by mass of thecomponent A is more than 200 parts by mass, the base material becomestoo soft and easily break, which is not preferable.

In addition, in the base material of the medical device of the presentinvention, a degree of crosslink is preferably in a range of 2.0 to18.3. The degree of crosslink is represented by the following formula(Q1).

$\begin{matrix}{{{DEGREE}\mspace{14mu}{OF}\mspace{14mu}{CROSSLINK}} = \frac{\sum\limits_{n = 1}^{\infty}\left\{ {{Qn} \times \left( {n - 1} \right)} \right\}}{\sum\limits_{n = 1}^{\infty}{Wn}}} & ({Q1})\end{matrix}$

In formula (Q1), Qn represents an amount of total milimol of a monomerhaving n polymerizable groups per molecule and Wn represents a totalmass (kg) of the monomer having n polymerizable groups per molecule.When a molecular weight of the monomer has distribution, the amount ofmilimol is determined to be calculated using a number average molecularweight.

When the degree of crosslink of the base material of the presentinvention is less than 2.0, the base material is too soft and handlingthereof becomes difficult, whereas, when the degree of crosslink exceeds18.3, the base material is too stiff and wearing feeling tends todeteriorate, which is not preferable. A more preferable range of thedegree of crosslink is 3.5 to 16.0; a further preferable range is 8.0 to15.0; and the most preferable range is 9.0 to 14.0.

As another aspect, the base material of the medical device of thepresent invention may be a hydrogel, and preferably a silicone hydrogelcontaining 5% by mass or more of silicon atoms.

In the medical device according to the present invention, a basematerial for hydrogel according to another aspect, at least a kind of acomponent S being a silicon monomer represented by the following generalformulae (s1) to (s2) is preferably included as a copolymer component.

In Formulae (s1) to (s2), R¹⁸ independently represents hydrogen or amethyl group. R¹⁹ represents an alkylene group having a carbon number of1 to 20 or an arylene group having a carbon number of 6 to 20, and a CH₂group in the alkylene group or the arylene group is optionallysubstituted with —O—, —S—, —CO—, —O—CO—, or —CO—O—. D represents asiloxanyl group.

As preferable example of R¹⁹, alkylene groups having a carbon number of1 to 20 optionally having one or more hydroxy group such as a methylenegroup, an ethylene group, a propylene group, an isopropylene group, abutylene group, a hydroxymethylene group, and a hydroxyethylene group;and arylene groups having a carbon number of 6 to 20 optionally havingone or more hydroxy group such as a phenylene group, a tolylene group, axylylene group, a naphthylene group, and a hydroxyphenylene group areexemplified. Furthermore, the CH₂ group in the alkylene group or thearylene group is optionally substituted with —O—, —S—, —CO—, —O—CO—, orby —CO—O—, and, for example, an acetylene group, —CH₂—O—C₃H₆—, and thelike are exemplified. Among them, an alkylene having a carbon number of2 to 5 and —CH₂—O—C₃H₆— are preferable and a propylene group and—CH₂—O—C₃H₆— are more preferable in that the silicone hydrogel easilysatisfies both low modulus and transparency.

A preferable example of D is a siloxanyl group represented by thefollowing formulae (d1) to (d3).

In formulae (d1) to (d3), R²⁰ to R²⁴ each independently represent asubstituent selected from an alkyl group having a carbon number of 1 to20 such as a methyl group, an ethyl group, a propyl group, and anisopropyl group or a substituent selected from an aryl group having acarbon number of 6 to 20 such as a phenyl group, a naphthyl group, andan anthracenyl group. n represents an integer of 1 to 50, and 2 to 20 ismore preferable, and 3 to 8 is the most preferable in that the siliconehydrogel satisfies both transparency and high oxygen permeability.

The component S is preferably silicone monomers represented by thefollowing formulae (t1) to (t4). The base material of the presentinvention preferably include at least one component S being siliconemonomers represented by the following formulae (t1) to (t4) as acopolymer component. In the medical device according to the presentinvention, a base material for hydrogel according to another aspect, thecomponent S may be used singly or in combination of two or more.

In the above formula (t2), n represents an integer of 3 to 200 (a massaverage molecular weight of about 500 to 15000).

A preferable example of the component S is acrylamide-based siliconemonomers disclosed in Japanese Translation of PCT Application No.2007-526364 and Japanese Patent Application Laid-open No. 10-212355.

In addition, in the medical device according to the present invention,the base material for hydrogel according to another aspect includes ahydrophilic component H as a copolymer component.

As a polymerizable functional groups in the hydrophilic component H ispreferably a radical polymerizable functional group and more preferablya functional group having a carbon-carbon double bond. Examples of thepreferable polymerizable functional group include a vinyl group, anallyl group, a (meth)acryloyl group, an α-alkoxymethylacryloyl group, amaleic acid residue, a fumaric acid residue, an itaconic acid residue, acrotonic acid residues, an isocrotonic acid residue, and a citraconicacid residue. Among them, the (meth)acryloyl group is the mostpreferable because the (meth)acryloyl group is highly polymerizable.

Preferable examples of the hydrophilic component H include methacrylicacid, acrylic acid, itaconic acid, 2-hydroxyethyl methacrylate,2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, 2-hydroxypropylacrylate, glycerol methacrylate, polyethylene glycol methacrylate,N,N-dimethyl acrylamide, N-methyl acrylamide, dimethylaminoethylmethacrylate, methylene-bis-acrylamide, diacetone acrylamide,N-vinylpyrrolidone, N-vinylcaprolactam, N-vinylacetamide, andN-vinyl-N-methylacetamide. Among them, the monomer having an amide groupsuch as N,N-dimethyl acrylamide, N-methyl acrylamide, dimethylaminoethylmethacrylate, methylene-bis-acrylamide, diacetone acrylamide,N-vinylpyrrolidone, N-vinylcaprolactam, N-vinylacetamide, andN-vinyl-N-methylacetamide are preferable from the viewpoint of a highlyhydrophilic property, and N,N-dimethyl acrylamide is the most preferablefrom the viewpoint of compatibility with the component S.

In the medical device according to the present invention, the basematerial for the hydrogel according to another aspect preferably furtherincludes a cross-linkable component I having two or more ofpolymerizable groups in one molecule. Preferable examples of thecross-linkable component I include ethylene glycol dimethacrylate,diethylene glycol dimethacrylate, triethylene glycol dimethacrylate,polyethylene glycol dimethacrylate, trimethylolpropane trimethacrylate,pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinylmethacrylate, acryl methacrylate, and acrylates corresponding to thesemethacrylates, divinyl benzene, and triallyl isocyanurate.

An amount of the hydrophilic component H to 100 parts by mass of thecomponent S is preferably 20 to 300 parts by mass, more preferably 25 to200 parts by mass, further preferably 30 to 150 parts by mass, and mostpreferably 30 to 80 parts by mass. When the used amount of thehydrophilic component H is too small, a water content of the basematerial becomes low and the base material becomes stiff. When the usedamount of the hydrophilic component is too large, the base materialtends to have white turbidity and deteriorate dimension stability due toincrease in evaporation of water from the base material surface.

A used amount of the cross-linkable component 1 to 100 parts by mass ofthe component S is preferably 0.01 to 20 parts by mass, more preferably0.05 to 10 parts by mass, further preferably 0.1 to 5 parts by mass, andmost preferably 0.5 to 4 parts by mass. When the amount of thecross-linkable component I is too small, shape stability of the basematerial deteriorates. When the amount of the cross-linkable componentis too large, the base material becomes stiff, and thus, wearing feelingbecomes worse particularly when the medical device is used as a softophthalmic lens.

In the medical device according to the present invention, the basematerial for hydrogel according to another aspect may further includecomponents (components Ck) such as an ultraviolet absorber, a dye, acolorant, a wetting agent, a slip agent, pharmaceutical andnutraceutical components, a compatibilizing component, an antimicrobialcomponent, and a release agent. Any of the components described abovemay be included in the form of a non-reactive component or in the formof a copolymer component.

When one or more of the components Ck are used, each of a total usedamounts of the components Ck to 100 parts by mass of the composition Sis preferably 0.00001 to 100 parts by mass, more preferably 0.0001 to 30parts by mass, and further preferably 0.001 to 5 parts by mass. When theused amount of the component Ck is too small, expected effects of thecomponent Ck such as ultraviolet absorption and coloring tend not to besufficiently obtained. When the used amount of the component Ck is toolarge, the obtained medical device tends to generate white turbidity,which is not preferable.

When the base material for hydrogel contains an ultraviolet absorber,body tissues of a wearer (an eye in the case of an ophthalmic lens) canbe protected from harmful ultraviolet. In addition, when the surfacecontains a colorant, the medical device is colored and the medicaldevice is easy to be distinguished, and therefore, convenience at thetime of handling is improved.

Any of the components described above may be included in the form of anon-reactive component or in the form of a copolymer component. When thecomponent described above is copolymerized, that is, when an ultravioletabsorber having a polymerizable functional group, a colorant having apolymerizable functional group, or the like is used, possibility ofelution is reduced because the component is copolymerized to the basematerial and immobilized, which is preferable.

The base material for hydrogel preferably includes components(components Ck) selected from the ultraviolet absorber and the colorant.

When the ultraviolet absorber is used, a used amount thereof to 100parts by mass of the component S is preferably 0.01 to 20 parts by mass,more preferably 0.05 to 10 parts by mass, and further preferably 0.1 to5 parts by mass. When the colorant is used, a used amount thereof to 100parts by mass of the component S is preferably 0.00001 to 5 parts bymass, more preferably 0.0001 to 1 parts by mass, and further preferably0.0001 to 0.5 parts by mass. When the content of the ultravioletabsorber or the colorant is too small, effect of the ultravioletabsorber or effect of the colorant is difficult to obtain. On thecontrary, when the content thereof is too large, it is difficult to makethese components dissolve in the base material.

As a method for producing the base material of the medical device, thatis, a lens-shaped or sheet-like molding, known methods can be used. Forexample, a method in which a rod or a plate-like polymer is obtained andthe polymer is processed in a desired shape by a cutting process or thelike, a mold polymerization method, a spin casting method, and the likecan be used. When the medical device is obtained by the cutting process,a freezing cutting under low temperature is preferable.

As one example, a method for producing an ophthalmic lens bypolymerizing a raw material composition of the base material using themold polymerization method will be described below. First, the rawmaterial composition is filled into a gap of two mold members having acertain shape. As a material for the mold members, a resin, a glass, aceramic, a metal, and the like are included. An optically transparentmaterial is preferably when photopolymerization is carried out, andtherefore, a resin or a glass is preferably used. Depending on a shapeof the mold members and properties of the raw material composition, agasket may be used in order to provide a constant thickness to anophthalmic lens and prevent liquid leakage of the raw materialcomposition filled in the gap. Subsequently, the mold of which the rawmaterial composition is filled in the gap is irradiated with active rayssuch as ultraviolet rays, visible light rays, or combination thereof, oris heated in an oven or a liquid bath to polymerize the filled rawmaterial composition. These two polymerization methods may be usedtogether at the same time. In other words, the heat polymerization maybe carried out after the photopolymerization or the photopolymerizationmay be carried out after the heat polymerization. As a specific aspectof the photopolymerization, for example, the raw material composition isirradiated with light including ultraviolet rays such as light of amercury lamp or a ultraviolet lamp (for example, FL15B, TOSHIBACORPORATION) for a short time (usually, 1 hour or less). When the heatpolymerization is carried out, conditions in which temperature of thecomposition gradually rises from room temperature and the temperature israised to 60° C. to 200° C. for several hours to several tens of hoursis preferable in order to maintain optical uniformity and quality of anophthalmic lens and improve repeatability.

In the polymerization, a heat polymerization initiator or aphotopolymerization initiator represented by a peroxide or an azocompound is preferably added in order to facilitate the polymerization.When the heat polymerization is carried out, the initiator havingoptimum decomposition properties at a desired reaction temperature isselected. In general, an azo initiator and a peroxide initiator having a10-hour half-life temperature of 40° C. to 120° C. are preferable. As aphotoinitiator when the photopolymerization is carried out, a carbonylcompound, a peroxide, an azo compound, a sulfur compound, a halogencompound, and a metal salt may be included. These polymerizationinitiators may be used singly or in combination. An amount of thepolymerization initiator is preferably up to 5% by mass at maximum tothe raw material composition.

When the polymerization is carried out, a polymerization solvent can beused. Various organic or inorganic solvents are applicable as thesolvent. Examples of the solvents include water; alcohols such as methylalcohol, ethyl alcohol, normal propyl alcohol, isopropyl alcohol, normalbutyl alcohol, isobutyl alcohol, t-butyl alcohol, t-amyl alcohol,tetrahydrolinalool, ethylene glycol, diethylene glycol, triethyleneglycol, tetraethylene glycol and polyethylene glycol; glycol ether-basedsolvents such as methyl cellosolve, ethyl cellosolve, isopropylcellosolve, butyl cellosolve, propylene glycol monomethyl ether,diethylene glycol monomethyl ether, triethylene glycol monomethyl ether,polyethylene glycol monomethyl ether, ethylene glycol dimethyl ether,diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, andpolyethylene glycol dimethyl ether; ester-based solvent such as ethylacetate, butyl acetate, amyl acetate, ethyl lactate, and methylbenzoate; aliphatic hydrocarbon solvents such as normal-hexane,normal-heptane, and normal-octane; alicyclic hydrocarbon solvents suchas cyclohexane and ethylcyclohexane; ketone-based solvents such asacetone, methyl ethyl ketone; and methyl isobutyl ketone; aromatichydrocarbon solvents such as benzene, toluene, and xylene; andpetroleum-based solvent. These solvents may be used singly or incombination of two or more.

The medical device of an embodiment of the present invention requiresthat a layer made of an acidic polymer and a basic polymer is formed(hereinafter, referred to as a coating layer) on at least a part of thesurface of the base material produced as described above. By having thecoating layer, excellent wettability and lubricity are provided on thesurface of the medical device, and therefore, excellent wearing feelingcan be provided.

The inventors of the present invention have found that a medical devicethat reduces a risk of bacterial proliferation and has excellentlubricity and wettability in a low water content base material can beprovided by forming a coating layer made of an acidic polymer and abasic polymer on the base material surface of the medical device of thepresent invention made by treating with a solution of at least a kind ofmulti-component copolymer of three or more components. In addition, theinventors of the present invention also have found that the medicaldevice that reduces lipid adhesion in a water containing hydrogel basematerial, particularly a silicone hydrogel base material.

The coating layer of the medical device of the present invention doesnot need to have a covalent bond between the coating layer and the basematerial. Because the production can be carried out by a simple process,it is preferable that the coating layer does not have a covalent bondbetween the base material and the coating layer. Without having acovalent bond between the base material and the coating layer, thecoating layer has a practical durability.

The coating layer is formed by treating the surface of the base materialwith an acidic polymer solution (the “solution” means an aqueoussolution) and a basic polymer solution (the “solution” means an aqueoussolution) that are described below in detail. Here, the aqueous solutionis a solution in which water is a main component.

The acidic polymer solution and the basic polymer solution of thepresent invention generally mean solutions including a kind of polymer(a kind means a polymer group in which the same monomers constitute thepolymer. A polymer synthesized in different formulation ratio is not akind even if the same monomers constitute the polymer). Even when asolution contains a kind (the same) of a polymer, solutions havingdifferent concentrations are not assumed as a kind.

The coating layer is preferably formed from one or more kinds of theacidic polymers and one or more kinds of the basic polymers. When two ormore kinds of the acidic polymers or two or more kinds of the basicpolymers are used, properties such as lubricity and antifoulingproperties are easily developed on the surface of the medical device,which is more preferable. The tendency is particularly enhanced when thetwo or more kinds of the acidic polymers and one or more kinds of thebasic polymers are used, which is further preferable.

The coating layer is preferably formed by carrying out treatment withone or more kinds of the acidic polymer solutions one or more times, andtreatment with one or more kinds of the basic polymer solutions one ormore times.

The coating layer is formed on the surface of the base material bycarrying out treatment with one or more kinds of the acidic polymersolutions and treatment with one or more kinds of the basic polymersolutions preferably each one to five times, more preferably each one tothree times, and further preferably each one to two times. The number oftimes of treatment with the acidic polymer solution and the number oftimes of treatment with the basic polymer solution may be different.

The coating layer is preferably formed on the surface of the basematerial by carrying out the treatment with one or more kinds of theacidic polymer solutions one or two times and treatment with one or morekinds of the basic polymer solutions one or two times, and consequently,carrying out the treatment three times in total.

The inventors of the present invention have found that, in the medicaldevice of the present invention, two or three times in total of thetreatment with one or more kinds of the acidic polymer solutions and thetreatment with one or more kinds of the basic polymer solutions, whichare extremely low times, excellent wettability and lubricity can beprovided. From the viewpoint of shortening in production processes, thishas significantly important meaning in industry. In this sense, in themedical device of the present invention, total times of the treatmentwith the acidic polymer solution and the treatment with the basicpolymer solution is preferably two or three times.

For the coating layer according to the medical device of the presentinvention, to carry out the treatment with two kinds of the acidicpolymer solutions one time each and treatment with the basic polymersolution one time is preferable.

The inventors of the present invention have ascertained that developmentof wettability and lubricity are hardly observed in the coating layer inwhich only treatment with either the acidic polymer solution or thebasic polymer solution is carried out.

As the acidic polymer used for the coating layer of the presentinvention, a homopolymer or a copolymer having a plurality of groupshaving acidity along the polymer chain can be preferably used. As thegroup having acidity, a carboxy group, a sulfonic acid group, aphosphoric acid group, and salts thereof are preferable, and the carboxygroup and the salt thereof are the most preferable. For example,preferable examples of such an acidic homopolymer includepolymethacrylic acid, polyacrylic acid, poly(vinylbenzoic acid),poly(thiophene-3-acetic acid), poly(4-styrenesulfonic acid),polyvinylsulfonic acid, poly(2-acrylamide-2-methylpropanesulfonic acid)and salts thereof.

When the acidic polymer is a copolymer, a copolymer including a monomerhaving one or more groups having acidity and polymerizable group in onemolecule (hereinafter referred to as an acidic monomer) is preferable.As the acidic monomer, a monomer having an allyl group, a vinyl group,and a (meth)acryloyl group as a polymerizable functional group ispreferable from the viewpoint of highly polymerizable property, and themonomer having the (meth)acryloyl group is the most preferable. Aspreferable acidic monomers constituting the copolymer, (meth)acrylicacid, vinylbenzoic acid, styrenesulfonic acid, vinylsulfonic acid,2-acrylamide-2-methylpropanesulfonic acid, itaconic acid, allylsulfonicacid, and salts thereof can be exemplified. Among them, (meth)acrylicacid, 2-acrylamide-2-methylpropanesulfonic acid, and the salts thereofare more preferable and (meth)acrylic acid and the salt thereof are themost preferable. As the acidic polymer used in the coating layer of thepresent invention, a copolymer using two or more kinds of the acidicmonomer selected from the above acidic monomers can be used.

The acidic polymer used in the coating layer of the present invention ispreferably a copolymer of the above acidic monomer and the monomerhaving a hydroxy group. When the copolymer of the monomer having ahydroxy group and the acidic monomer is used as the coating layer, therisk of the bacterial proliferation can be reduced because theantifouling property to a lacrimal fluid can be improved. The monomerhaving a hydroxy group means a monomer having one or more hydroxy groupand a radically polymerizable functional group in one molecule. Theradically polymerizable functional group is preferably a functionalgroup having a carbon-carbon double bond, and examples of the radicallypolymerizable functional group include a vinyl group, an allyl group, a(meth)acryloyl group, an α-alkoxymethylacryloyl group, a maleic acidresidue, a fumaric acid residue, an itaconic acid residue, a crotonicacid residues, an isocrotonic acid residues, and a citraconic acidresidue, and, in terms of ease of polymerization, the monomer having the(meth)acryloyl groups is preferable.

Preferable examples of the monomer having a hydroxy group includehydroxyethyl(meth)acrylate, hydroxypropyl(meth)acrylate,hydroxybutyl(meth)acrylate, hydroxyethyl(meth)acrylamide,glycerol(meth)acrylate, caprolactonemodified-2-hydroxyethyl(meth)acrylate, N-(4-hydroxyphenyl)maleimide,hydroxystyrene, and vinyl alcohol (a carboxylic acid vinyl ester as aprecursor). As the monomer having a hydroxy group,hydroxyethyl(meth)acrylate, hydroxypropyl(meth)acrylate, andglycerol(meth)acrylate are preferable and, among them,hydroxyethyl(meth)acrylate is the most preferable.

Preferable specific examples of the copolymer of the acidic monomer andthe monomer having a hydroxy group include a (meth)acrylicacid/hydroxyethyl(meth)acrylate copolymer, a (meth)acrylicacid/glycerol(meth)acrylate copolymer, a2-acrylamide-2-methylpropanesulfonic acid/hydroxyethyl(meth)acrylatecopolymer, and a 2-acrylamide-2-methylpropanesulfonicacid/glycerol(meth)acrylate copolymer. The (meth)acrylicacid/hydroxyethyl(meth)acrylate copolymers are the most preferable.

As polymers exerting similar effect to the copolymer of the acidicmonomer and the monomer having a hydroxy group, polymers having afunctional group having acidity and a hydroxy group are exemplified, andfor example, when a polysaccharide having an acidic group such ashyaluronic acid, chondroitin sulfate, carboxymethyl cellulose, andcarboxypropyl cellulose is used as the coating layer, the antifoulingproperty for the lacrimal fluid can be improved.

The acidic polymer used in the coating layer of the present invention ispreferably a copolymer of the above acidic monomer and the monomerhaving an amide group. When a copolymer of the monomer having an amidegroup and the acidic monomer are used as the coating layer, wettabilityand lubricity can be improved because the copolymer can improve ahydrophilic property compared with the homopolymer of the acidicmonomer. The monomer having an amide group means a monomer having one ormore amide group and radically polymerizable functional group in onemolecule. The radically polymerizable functional group is preferable afunctional group having a carbon-carbon double bond, and examples of theradically polymerizable functional group include a vinyl group, an allylgroup, a (meth)acryloyl group, an α-alkoxymethyl acryloyl group, amaleic acid residue, a fumaric acid residue, an itaconic acid residue, acrotonic acid residues, an isocrotonic acid residues, and a citraconicacid residue, and, in terms of ease of polymerization, the monomerhaving the (meth)acrylamide groups or N-vinylcarboxylic acid amide(including a cyclic amide) are preferable.

Preferable examples of the monomer having an amide group includeN-vinylpyrrolidone, N-vinylcaprolactam, N-vinylacetamide,N-methyl-N-vinylacetamide, N-vinylformamide, N,N-dimethylacrylamide,N,N-diethylacrylamide, N-isopropylacrylamide,N-(2-hydroxyethyl)acrylamide, acryloylmorpholine, and acrylamide. Amongthe monomers having an amide group, N-vinylpyrrolidone andN,N-dimethylacrylamide are preferable, and N,N-dimethylacrylamide is themost preferable.

Preferable examples of the copolymer of the acidic monomer and themonomer having an amide group include a (meth)acrylicacid/N-vinylpyrrolidone copolymer, a (meth)acrylicacid/N,N-dimethylacrylamide copolymer, a2-acrylamide-2-methylpropanesulfonic acid/N-vinylpyrrolidone copolymer,and a 2-acrylamide-2-methylpropanesulfonic acid/N,N-dimethylacrylamidecopolymer. The most preferable is the (meth)acrylicacid/N,N-dimethylacrylamide copolymer. As polymers exerting similareffect to the copolymer of the acidic monomer and the monomer having anamide group, polymers having a functional group having acidity and anamide group are exemplified, and for example, sialic acid can beincluded.

When the copolymer of two components of the acidic monomer and anothermonomer is used, a copolymerization ratio of these [Number of moles ofacidic monomer]/[Number of moles of another monomer] is preferably 1/99to 99/1, more preferably 2/98 to 90/10, and further preferably 10/90 to80/20. When the copolymerization ratio is in this range, functions suchas the lubricity and the antifouling property to the lacrimal fluid canbe easily developed.

The acidic polymer used in the coating layer of the present invention ispreferably a multi-component copolymer containing three or morecomponents. When the multi-component copolymer is used, when [Totalnumber of moles of acidic monomer]/[Total number of moles of monomersother than acidic monomer] is too small, adhering property of thecoating layer is deteriorated, whereas, when the ratio is too large,effects of the antifouling properties and the water solubility, whichare expected to other monomers, is deteriorated, and therefore, theratio is preferably 2/1 to 1/9, more preferably 1/1 to 1/7, and furtherpreferably 1/1 to 1/5. A preferable copolymerization ratio when themonomers other than the acidic monomer in the multi-component copolymerare divided into water soluble monomers and water insoluble monomers is,because water solubility of the multi-component copolymer isdeteriorated when [Total number of moles of water insolublemonomer]/[Total number of moles of water soluble monomer] is too large,preferably 0/1 to 4/1, more preferably 0/1 to 1/1, and most preferably0/1 to 1/4. Here, the “water soluble monomer” in the present inventionrepresents a monomer that exhibits homogeneous appearance withoutseparation when water and the monomer in a ratio of 1:1 are mixed atroom temperature and, after stirring, the mixture was left to stand for1 minute or more, whereas the “water insoluble monomer” represents amonomer that is separated from water under the conditions describedabove. When the copolymerization ratio of three or more monomers is inthis range, functions such as the lubricity and the antifouling propertyto the lacrimal fluid are easily developed.

The acidic polymer used for the coating layer of the present inventionis further preferably a copolymer of three components of the acidicmonomer, the monomer having a hydroxy group, and the monomer having anamide group. When the copolymer of three components of the acidicmonomer, the monomer having a hydroxy group, and the monomer having anamide group is used as the coating layer, the risk of the bacterialproliferation can be reduced by improving the antifouling property aswell as wettability and lubricity can be improved.

Specific preferable examples of the copolymer of three components of theacidic monomer, the monomer having a hydroxy group, and the monomerhaving an amide group include a (meth)acrylicacid/hydroxyethyl(meth)acrylate/N-vinylpyrrolidone copolymer, a(meth)acrylic acid/hydroxyethyl(meth)acrylate/N,N-dimethylacrylamidecopolymer, a (meth)acrylicacid/glycerol(meth)acrylate/N-vinylpyrrolidone copolymer, a(meth)acrylic acid/glycerol(meth)acrylate/N,N-dimethylacrylamidecopolymer, a 2-acrylamide-2-methylpropanesulfonicacid/hydroxyethyl(meth)acrylate/N-vinylpyrrolidone copolymer, and a2-acrylamide-2-methylpropanesulfonicacid/hydroxyethyl(meth)acrylate/N,N-dimethylacrylamide copolymer. Themost preferable is the (meth)acrylicacid/hydroxyethyl(meth)acrylate/N,N-dimethylacrylamide copolymer.

When the copolymer of three components of the acidic monomer, themonomer having a hydroxy group, and the monomer having an amide group isused, the adhering property of the coating layer is deteriorated when[Number of moles of acidic monomer]/{[Number of moles of monomer havinga hydroxy group]+[Number of moles of monomer having an amide group]} istoo small, whereas effect of the antifouling property, which is expectedto the monomer having a hydroxy group and the monomer having an amidegroup, is deteriorated when the ratio is too large, and therefore, theratio is preferably 2/1 to 1/9, more preferably 1/1 to 1/7, and furtherpreferably 1/1 to 1/5. When [Number of moles of monomer having a hydroxygroup]/[Number of moles of monomer having an amide group] in thecopolymer of three components is too small, a sufficient antifoulingproperty is not obtained, whereas, when the ratio is too large, watersolubility is deteriorated, and therefore, the ratio is preferably 5/1to 1/5, more preferably 3/1 to 1/4, and most preferably 1/1 to 1/3. Whenthe copolymerization ratio of the copolymer of three components is inthis range, functions such as the lubricity and the antifouling propertyto the lacrimal fluid are easily developed.

Another preferable aspect of the acidic polymer used for the coatinglayer of the present invention is a copolymer of three components of theacidic monomer and two kinds of monomers having an amide group. In thecase of using the copolymer of three components, when [Number of molesof acidic monomer]/[Total number of moles of two monomers having amidegroups] is too small, adhesion of the coating layer is deteriorated,whereas, when the ratio is too large, effects of the antifoulingproperty and the water solubility, which is expected to the monomerhaving an amide group, are deteriorated, and therefore, the ratio ispreferably 2/1 to 1/9, more preferably 1/1 to 1/7, and furtherpreferably 1/1 to 1/5. In addition, a preferable copolymerization ratioof the two monomers having an amide group in the copolymer of threecomponents is preferably 1/99 to 99/1, more preferably 10/90 to 90/10,and most preferably 20/80 to 80/20, because a sufficient antifoulingproperty and the water solubility may not be obtained when [Number ofmoles of monomer having an amide group]/[Number of moles of two monomershaving amide groups] is too small or too large. When thecopolymerization ratio of the copolymer of three components is in thisrange, functions such as the lubricity and the antifouling property tothe lacrimal fluid are easily developed.

Another preferable aspect of the acidic polymer used for the coatinglayer of the present invention is a copolymer of four or morecomponents. When [Number of moles of acidic monomer]/[Total number ofmoles of monomers other than acidic monomer] in the case of using thecopolymer of four or more components is too small, adhesion of thecoating layer is deteriorated, whereas, when the ratio is too large,effects of the antifouling property and the water solubility, which isexpected to the other monomer, are deteriorated, and therefore, theratio is preferably 2/1 to 1/9, more preferably 1/1 to 1/7, and furtherpreferably 1/1 to 1/5. A preferable copolymerization ratio when themonomers other than the acidic monomer in the multi-component copolymerof four components or more are divided into water soluble monomers andwater insoluble monomers is preferably 0/1 to 4/1, more preferably 0/1to 1/1, and most preferably 0/1 to 1/4 because water solubility of themulti-component copolymer is deteriorated when [Total number of moles ofwater insoluble monomers]/[Total number of moles of water solublemonomers] is too large. When a copolymerization ratio of four or moremonomers is in this range, functions such as the lubricity and theantifouling property to the lacrimal fluid are easily developed.

As the basic polymer used for the coating layer of the presentinvention, a homopolymer or a copolymer having a plurality of groupshaving basicity along the polymer chain can be preferably used. As thegroup having basicity, an amino group and a salt thereof are preferable.For example, preferable examples of the basic homopolymer include aminogroup-containing (meth)acrylate polymers such as poly(allylamine),poly(vinylamine), poly(ethyleneimine), poly(vinylbenzyltrimethylamine),polyaniline, poly(aminostyrene), poly(N,N-dialkylaminoethylmethacrylate), amino group-containing (meth)acrylamide polymers such aspoly(N,N-dimethylaminopropyl acrylamide), and salts thereof.

When the basic polymer is a copolymer, a copolymer including a monomerhaving one or more of a group having basicity and polymerizablefunctional group in one molecule (hereinafter referred to as a basicmonomer) is preferable. As the basic monomer constituting the copolymer,a monomer having an allyl group, a vinyl group, and a (meth)acryloylgroup as a polymerizable functional group is preferable in terms of highpolymerizable property, and the monomer having the (meth)acryloyl groupis the most preferable. As preferable basic monomers constituting thecopolymer, allylamine, vinylamine (N-vinylcarboxylic acid amide as aprecursor), vinylbenzyltrimethylamine, amino group-containing styrene,amino group-containing (meth)acrylate, amino group-containing(meth)acrylamide, and salts thereof can be exemplified. Among them,amino group-containing (meth)acrylate, amino group-containing(meth)acrylamide, and the salts thereof are more preferable in terms ofhigh polymerization property, and N,N-dimethylaminoethyl methacrylate,N,N-dimethylaminopropyl acrylamide, and the salts thereof are the mostpreferable. As the basic polymer used in the coating layer of thepresent invention, a copolymer using two or more kinds of the basicmonomer selected from the above basic monomers can be used.

The basic polymer may be a polymer having a quaternary ammoniumstructure. When the polymer compound having the quaternary ammoniumstructure is used for coating of the medical device, an antimicrobialproperty can be provided to the medical device.

The basic polymer used in the coating layer of the present invention ispreferably a copolymer of the above basic monomer and the monomer havinga hydroxy group. When the copolymer of the monomer having a hydroxygroup and the basic monomer is used as the coating layer, the risk ofthe bacterial proliferation can be reduced because the antifoulingproperty to body fluids such as the lacrimal fluid can be improved.

Preferable specific examples of the copolymer of the basic monomer andthe monomer having a hydroxy group include an N,N-dimethylaminoethylmethacrylate/hydroxyethyl(meth)acrylate copolymer, anN,N-dimethylaminoethyl methacrylate/glycerol(meth)acrylate copolymer,N,N-dimethylaminopropyl acrylamide/hydroxyethyl(meth)acrylate copolymer,and an N,N-dimethylaminopropyl acrylamide/glycerol(meth)acrylatecopolymer. The most preferable is the N,N-dimethylaminoethylmethacrylate/hydroxyethyl(meth)acrylate copolymer.

As polymers exerting similar effect to the copolymer of the basicmonomer and the monomer having a hydroxy group, aminopolysaccharidessuch as chitin, which are polymers having a functional group havingbasicity and a hydroxy group, can be included.

The basic polymer used in the coating layer of the present invention ispreferably a copolymer of the above basic monomer and the monomer havingan amide group. When a copolymer of the monomer having an amide groupand the basic monomer are used as the coating layer, wettability andlubricity can be improved because the copolymer can improve ahydrophilic property compared with the homopolymer of the basic monomer.

Preferable specific examples of the copolymer of the basic monomer andthe monomer having an amide group include an N,N-dimethylaminoethylmethacrylate/N-vinylpyrrolidone copolymer, an N,N-dimethylaminoethylmethacrylate/N,N-dimethylacrylamide copolymer, anN,N-dimethylaminopropyl acrylamide/N-vinylpyrrolidone copolymer, and anN,N-dimethylaminopropyl acrylamide/N,N-dimethylacrylamide copolymer. Themost preferable is the N,N-dimethylaminopropylacrylamide/N,N-dimethylacrylamide copolymer.

When a copolymer of two components of the basic monomer and anothermonomer is used, a copolymerization ratio of these [Number of moles ofbasic monomer]/[Number of moles of another monomer] is preferably 1/99to 99/1, more preferably 2/98 to 90/10, and further preferably 10/90 to80/20. When the copolymerization ratio is in this range, functions suchas lubricity and an antifouling property to a lacrimal fluid can beeasily developed.

As polymers exerting similar effect to the copolymer of the basicmonomer and the monomer having an amide group, partially hydrolyzedchitosan, which is a polymer having a functional group having basicityand an amide group, can be included.

The basic polymer used for the coating layer of the present invention ispreferably a multi-component copolymer of three or more components. Whenthe multi-component copolymer is used, when [Total number of moles ofbasic monomer]/[Total number of moles of monomers other than basicmonomer] is too small, adhering property of the coating layer isdeteriorated, whereas, when the ratio is too large, effects of theantifouling property and water solubility, which are expected to othermonomers are deteriorated, and therefore, the ratio is preferably 2/1 to1/9, more preferably 1/1 to 1/7, and further preferably 1/1 to 1/5. Apreferable copolymerization ratio when the monomers other than the basicmonomer in the multi-component copolymer of three or more components aredivided into water soluble monomers and water insoluble monomers ispreferably 0/1 to 1/5, more preferably 0/1 to 1/4, and most preferably5/1 to 1/3 because water solubility of the multi-component copolymer isdeteriorated when [Total number of moles of water insolublemonomers]/[Total number of moles of water soluble monomers] is toolarge. Here, the “water soluble monomer” in the present inventionrepresents a monomer that exhibits homogeneous appearance withoutseparation when water and the monomer in a volume ratio of 1:1 are mixedat room temperature and, after stirring, the mixture was left to standfor 1 minute or more, whereas the “water insoluble monomer” represents amonomer that is separated from water under the conditions describedabove. When the copolymerization ratio of three or more monomers is inthis range, functions such as the lubricity and the antifouling propertyto the lacrimal fluid are easily developed.

The basic polymer used for the coating layer of the present invention isfurther preferably a copolymer of three components of the basic monomer,the monomer having a hydroxy group, and the monomer having an amidegroup. When the copolymer of three components of the basic monomer, themonomer having a hydroxy group, and the monomer having an amide group isused as the coating layer, the risk of the bacterial proliferation canbe reduced by improving the antifouling property as well as wettabilityand lubricity can be improved.

Preferable specific examples of the copolymer of three components of thebasic monomer, the monomer having a hydroxy group, and the monomerhaving an amide group include an N,N-dimethylaminoethylmethacrylate/hydroxyethyl(meth)acrylate/N-vinylpyrrolidone copolymer, anN,N-dimethylaminoethylmethacrylate/hydroxyethyl(meth)acrylate/N,N-dimethylacrylamidecopolymer, an N,N-dimethylaminoethylmethacrylate/glycerol(meth)acrylate/N-vinylpyrrolidone copolymer, anN,N-dimethylaminoethylmethacrylate/glycerol(meth)acrylate/N,N-dimethylacrylamide copolymer, anN,N-dimethylaminopropylacrylamide/hydroxypropyl(meth)acrylate/N-vinylpyrrolidone copolymer, andan N,N-dimethylaminopropylacrylamide/hydroxypropyl(meth)acrylate/N,N-dimethylacrylamide copolymer.The most preferable is the N,N-dimethylaminopropylacrylamide/hydroxypropyl(meth)acrylate/N,N-dimethylacrylamide copolymer.

When a terpolymer of a basic monomer, a monomer having a hydroxy group,and a monomer having an amide group is used, the adhering property ofthe coating layer is deteriorated when a copolymerization ratio of these[Number of moles of basic monomer]/{[Number of moles of monomer having ahydroxy group]+[Number of moles of monomer having an amide group]} istoo small, whereas effect of the antifouling properties, which isexpected to the monomer having a hydroxy group and the monomer having anamide group, is deteriorated when the ratio is too large, and therefore,the ratio is preferably 2/1 to 1/9, more preferably 1/1 to 1/7, andfurther preferably 1/1 to 1/5. When [Number of moles of monomer having ahydroxy group]/[Number of moles of monomer having an amide group] in theterpolymer is too small, sufficient antifouling properties are notobtained, whereas, when the ratio is too large, the water solubility isdeteriorated, and therefore, the ratio is preferably 5/1 to 1/5, morepreferably 3/1 to 1/4, and most preferably 1/1 to 1/3. When thecopolymerization ratio of the terpolymer is in this range, functionssuch as the lubricity and the antifouling properties to the lacrimalfluid are easily developed.

Another preferable aspect of the basic polymer used for the coatinglayer of the present invention is a copolymer of three components of thebasic monomer and two kinds of monomers having an amide group. In thecase of using the copolymer of three components, when [Number of molesof basic monomer]/[Total number of moles of two monomers having amidegroups] is too small, the adhering property of the coating layer isdeteriorated, whereas, when the ratio is too large, effects of theantifouling property and the water solubility, which are expected to themonomer having an amide group, are deteriorated, and therefore, theratio is preferably 2/1 to 1/9, more preferably 1/1 to 1/7, and furtherpreferably 1/1 to 1/5. In addition, a preferable copolymerization ratioof the two monomers having an amide group in the copolymer of threecomponents is preferably 1/99 to 99/1, more preferably 10/90 to 90/10,and most preferably 20/80 to 80/20, because a sufficient antifoulingproperty and the water solubility may not be obtained when [Number ofmoles of monomer having an amide group]/[Number of moles of two monomershaving amide groups] is too small or too large. When thecopolymerization ratio of the copolymer of three components is in thisrange, functions such as the lubricity and the antifouling property tothe lacrimal fluid are easily developed.

Another preferable aspect of the basic polymer used for the coatinglayer of the present invention is a copolymer of four or morecomponents. In the case of using the copolymer of four or morecomponents, when [Number of moles of basic monomer]/[Total number ofmoles of monomers other than basic monomer] is too small, the adheringproperty of the coating layer is deteriorated, whereas, when the ratiois too large, effects of the antifouling property and the watersolubility, which are expected to the other monomers, are deteriorated,and therefore, the ratio is preferably 2/1 to 1/9, more preferably 1/1to 1/7, and further preferably 1/1 to 1/5. A preferable copolymerizationratio when the monomers other than the basic monomer in themulti-component copolymer of four components or more are divided intowater soluble monomers and water insoluble monomers is preferably 0/1 to1/5, more preferably 0/1 to 1/4, and most preferably 5/1 to 1/3 becausewater solubility of the multi-component copolymer is deteriorated when[Total number of moles of water insoluble monomers]/[Total number ofmoles of water soluble monomers] is too large. When the copolymerizationratio of four or more monomers is in this range, functions such as thelubricity and the antifouling property to the lacrimal fluid are easilydeveloped.

As a method for producing the acidic polymer and the basic polymer beingthe coating layer of the medical device, the known methods can be used.For example, in the predetermined ratio described above, monomers areformulated in a solvent and a polymerization initiator is added, andthereafter, a polymerization reaction is carried out at a predeterminedtemperature under presence of an inert medium with refluxing. Thereacted substance obtained by the reaction is immersed into a solvent toremove non-reacted monomer components, and thereafter, the substance iswashed and dried to obtain a polymer. By this method, a homopolymer or acopolymer of two components or three or more components can be produced.

In order to change various properties, for example the thickness, of thecoating layer, molecular weights of the acidic polymer and the basicpolymer can be changed. Specifically, when the molecular weightincreases, the thickness of the coating layer generally increases. Whenthe molecular weight is too large, however, handling may becomedifficult due to increase in viscosity. Therefore, each of the acidicpolymer and the basic polymer used in the present invention preferablyhas a molecular weight of 2000 to 2000000. Each of the molecular weightis more preferably 5000 to 1000000 and further preferably 7500 to700000. The molecular weight of the acidic polymer and the basic polymeris a mass average molecular weight in terms of polyethylene glycolmeasured with a gel permeation chromatography method (water-basedsolvent).

Application of the coating layer can be achieved by many methods asdescribed in, for example, WO 99/35520, WO 01/57118, the disclosure ofwhich is incorporated herein by reference, and U.S. Pat. No.2001-0045676, the disclosure of which is incorporated herein byreference.

In the medical device of an embodiment of the present invention, a layermade of the acidic polymer and a layer made of the basic polymer(hereinafter referred to as a coating layer) is formed on at least apart of the base material surface, and at least a part of the layer maybe crosslinked. In the medical device of the present invention, at leasta part between the above base material and the above layer may becrosslinked. Here, the crosslink means that polymers form a crosslinkingstructure using their own functional groups or a crosslinking agent tobond each other.

The above crosslink can be generated by irradiating with radiation raysin a state that at least the acidic polymer and the basic polymer adhereto the base material. The radiation rays preferably include various ionbeams, electron beams, positron beams, X rays, γ rays, and neutronbeams, and more preferably electron beams and γ rays. The mostpreferable is γ rays.

By generating crosslink in the coating layer or between the coatinglayer and the base material as described above, excellent wettabilityand lubricity can be provided on a surface of a lens, and therefore,excellent wearing feeling can be provided. On the other hand, thecrosslink may also be generated inside of the base material byirradiating with radiation rays, and therefore, the medical device maybecome too stiff. In this case, for a low water content base material,excess crosslink of inside of the base material can be reduced bycarrying out copolymerization in a manner that the component A in thebase material is adequately replaced to the component M. For awater-containing base material, excess crosslink of inside of the basematerial can be reduced by carrying out copolymerization in a mannerthat the cross-linkable component I in the base material is adequatelyreplaced to the component S or the hydrophilic component H.

Subsequently, a method for producing the medical device of the presentinvention will be described. The medical device of the present inventionis obtained by applying one or more kinds of the acidic polymersolutions and one or more kinds of the basic polymer solutions eachpreferably one to five times, more preferably one to three times, andfurther preferably one to two times to a surface of a lens-shaped orsheet-like molding (a base material) to form a coating layer. The numberof times of application processes of the acidic polymer solution and thenumber of times of application processes of the basic polymer solutionmay be different.

The inventors of the present invention have found that excellentwettability and lubricity can be provided in a very small number oftimes of application processes of one or more kinds of the acidicpolymer solutions and application processes of one or more kinds of thebasic polymer solutions, which is two or three times in total. From theviewpoint of shortening in production processes, this has significantlyimportant meaning in industry.

The inventors of the present invention is ascertained at the same timethat, in the medical device of the present invention, only either theapplication process of the acidic polymer solution or the applicationprocess of the basic polymer solution is carried out one time,development of wettability and lubricity is hardly observed.

In the medical device of the present invention, from the viewpoint ofthe wettability, the lubricity, the antifouling property, and theshortening in production process, application of the coating layer ispreferably carried out in constitutions selected from the followingconstitution 1 to 4. In the following description, each application stepto a surface of a molding is sequentially carried out from the leftside.

Constitution 1: Application of basic polymer solution/application ofacidic polymer solution

Constitution 2: Application of acidic polymer solution/application ofbasic polymer solution

Constitution 3: Application of basic polymer solution/application ofacidic polymer solution/application of basic polymer solution

Constitution 4: Application of acidic polymer solution/application ofbasic polymer solution/application of acidic polymer solution

Among these constitutions, the constitution 1 and the constitution 4 arepreferable and the constitution 4 is more preferable because theobtained medical device exhibits particularly excellent wettability andantifouling property.

In the coating layer of the medical device of the present invention, inthe above constitution 1 to constitution 4, at least a kind of theacidic polymer or the basic polymer used in each application process ispreferably a multi-component copolymer of three or more components. Asthe multi-component copolymer of three or more components, thecopolymers exemplified above can be used. Preferably, a final processsolution contains the multi-component copolymer of three or morecomponents. However, process solutions for first or second treatment maycontain the multi-component copolymer of three or more components.

As the coating layer of the medical device of the present invention, inthe constitution 1 to constitution 4, at least a kind of the acidicpolymer and the basic polymer used in each application process ispreferably a polymer having a group selected from a hydroxy group and anamide group, and two or more of the acidic polymer and the basic polymerare polymers having groups selected from a hydroxy group and an amidegroup.

As the coating layer of the medical device of the present invention, inthe constitution 1 to constitution 4, at least a kind of the acidicpolymer and the basic polymer used in each application process is amulti-component copolymer of three or more components and themulti-component copolymer of three or more components is preferably apolymer having a group selected from a hydroxy group and an amide group.In addition, two or more of polymers among the acidic polymer and thebasic polymer are multi-component copolymers of three or more componentsand the multi-component copolymers of three or more components arepreferably polymers having groups selected from a hydroxy group and anamide group.

As the coating layer of the medical device of the present invention, inthe constitution 1 to constitution 4, at least a kind of the acidicpolymer and the basic polymer used in each application process ispreferably a polymer having a hydroxy group.

As the coating layer of the medical device of the present invention, inthe constitution 1 to constitution 4, at least a kind of the acidicpolymer and the basic polymer used in each application process ispreferably a multi-component copolymer of three or more componentscontaining one or more kinds of each of the monomer having a hydroxygroup and the monomer having an amide group.

In the above production method, any one kind of the acidic polymer andthe basic polymer used in the above step 2 or 3 is preferably amulti-component copolymer of three or more components.

In the coating layer of the medical device of the present invention, inthe constitution 1 to the constitution 4, one or more kinds of the basicpolymer solutions and/or one or more kinds of the acidic polymersolutions can be used. For example, the acidic polymer solution that isused for first and third treatment in the constitution 4 may be the samekind and the same concentration (or different concentrations) of theacidic polymer solution or different kinds of the acidic polymersolutions may be used.

When the acidic polymer solution and the basic polymer solution areapplied, the surface of the base material may be an untreated or atreated surface. Here, that the surface of the base material is atreated surface means that surface treatment or surface modification iscarried out to the surface of the base material by known methods.Preferable examples of the surface treatment or the surface modificationinclude plasma treatment, chemical modification, chemicalfunctionalization, and plasma coating.

One of the preferable aspects of the production method (aspect P1) ofthe medical device of the present invention is a method including thefollowing step 1 to step 3 in this order:

<Step 1>

polymerizing a mixture including a monomer having a siloxanyl group toobtain a molding;

<Step 2>

contacting the molding to a basic polymer solution, and thereafter,washing and removing the excessive basic polymer solution; and

<Step 3>

contacting the molding to an acidic polymer solution, and thereafter,washing and removing the excessive acidic polymer solution.

In the production method described above, any one kind of the acidicpolymer and the basic polymer used in the step 2 or 3 is preferably amulti-component copolymer of three or more components.

One of the preferable aspects (Aspect P2) of the production method ofthe medical device of the present invention is a method including thefollowing step 1 to step 4 in this order:

<Step 1>

polymerizing a mixture including a monomer having a siloxanyl group toobtain a molding;

<Step 2>

contacting the molding to an acidic polymer solution, and thereafter,washing and removing the excessive acidic polymer solution;

<Step 3>

contacting the molding to a basic polymer solution, and thereafter,washing and removing the excessive basic polymer solution; and

<Step 4>

contacting the molding to an acidic polymer solution being the same asor different from the acidic polymer in step 2, and thereafter, washingand removing the excessive acidic polymer solution.

In the above production method, any one kind of the acidic polymer andthe basic polymer used in the above steps 2 to 4 is preferably amulti-component copolymer of three or more components.

In addition, one of the preferable aspects (Aspect P3) of the productionmethod of the medical device of the present invention is a methodincluding the following step 1 to step 4 in this order:

<Step 1>

polymerizing a mixture including a monomer having a siloxanyl group toobtain a molding;

<Step 2>

contacting the molding to an acidic polymer solution, and thereafter,washing and removing the excessive acidic polymer solution;

<Step 3>

contacting the molding to a basic polymer solution, and thereafter,washing and removing the excessive basic polymer solution; and

<Step 4>

contacting the molding to an acidic polymer solution made of amulti-component copolymer of three or more components, and thereafter,washing and removing the excessive acidic polymer solution.

The step 1 in the aspect P1 to the aspect P3 is preferably “a step foris copolymerizing a mixture including a component A that has a pluralityof polymerizable functional groups in one molecule and is a polysiloxanecompound having a number average molecular weight of 6000 or more and acomponent B that is a polymerizable monomer having a fluoroalkyl groupto obtain a molding”.

In addition, the step 1 in the aspect P1 to the aspect P3 is preferably“a step for copolymerizing a mixture including a component S being amonomer having a polymerizable functional group and a siloxanyl groupper molecule to obtain a molding made of a silicone hydrogel containing5% by mass or more of silicon atoms”.

As described above, by sequentially contacting the molding to the acidicpolymer solution and the basic polymer solution, a layer made of theacidic polymer and the basic polymer can be formed on the molding.Thereafter, preferably, the excessive polymer is sufficiently washed andremoved.

As a method for contacting the molding to the acidic polymer solution orthe basic polymer solution, various coating methods such as an immersionmethod (a dipping method), a brush coating method, a spray coatingmethod, a spin coat method, a die coat method, and a squeegee method canbe applied.

When the contact to the solution is carried out by the immersion method,an immersion time can be changed depending on many factors. Immersion ofthe molding to the acidic polymer solution or the basic polymer solutionis carried out for preferably 1 to 30 minutes, more preferably 2 to 20minutes, and most preferably 1 to 5 minutes.

A concentration of the acidic polymer solution and the basic polymersolution can be changed depending on properties of the acidic polymersolution and the basic polymer solution, desired thicknesses of thecoating layer, and other many factors. A concentration of the acidicpolymer and the basic polymer is preferably 0.001 to 10% by mass, morepreferably 0.005 to 5% by mass, and most preferably 0.01 to 3% by mass.

As pH of the acidic polymer solution and the basic polymer solution, itis preferable that the pH is maintained preferably 2 to 6, morepreferably 2 to 5, and further preferably 2.5 to 4.5 in the case of theacidic polymer solution whereas it is preferable that the pH ismaintained preferably 8 to 12, more preferably 9 to 12, furtherpreferably 9.5 to 11.5 in the case of the basic polymer solution.

Washing and removal of the excessive acidic polymer and basic polymer iscarried out by rinsing the molding after coating generally using cleanwater or an organic solvent. The rinse is preferably carried out byimmersing the molding to water or an organic solvent or exposing themolding to water flow or organic solvent flow. Although the rinse may becompleted in one process, it has been found that carrying out aplurality of rinse processes is more effective. The rinse is preferablycarried out in 2 to 5 processes. Each molding is preferably immersed toa rinsing solution for 1 to 3 minutes.

Although pure water is preferable for the rinsing solution, a bufferedaqueous solution having a pH of preferably 2 to 7, more preferably 2 to5, and further preferably 2.5 to 4.5 is preferably used in order toimprove adhesion of the coating layer.

A process for drying or removing an excessive rinsing solution may beincluded. The molding can be dried to some extent by simply leaving tostand the molding under atmosphere. The drying, however, is preferablyaccelerated by blowing moderate air flow to the surface. A flow rate ofthe air flow can be adjusted as a function of strength of a material tobe dried and fixturing of the material. The molding does not need to befully dried. Here, removal of droplets of the solution adhering to themolding surface is rather important than the drying of the molding.Therefore, the drying may be carried out to the extent that only a filmof water or the solution on the molding surface is removed, and this ispreferable because of reduction in process time.

As described in the constitution 1 to the constitution 4, the acidicpolymer and the basic polymer are preferable alternately applied on themolding. By alternately applying, the medical device having excellentwettability and lubricity, which cannot be obtained by either of theapplication processes alone, and further excellent wearing feeling canbe obtained.

In the medical device of the present invention, the coating layer may beasymmetry. Here, the “asymmetry” means that the medical device hasdifferent coating layers on a first surface and an opposite secondsurface. Here, the “different coating layers” mean that the coatinglayer formed in the first surface and the coating layer formed on thesecond surface have different surface characteristics orfunctionalities.

The thickness of the coating layer can be adjusted by adding one or moresalt such as sodium chloride to the acidic polymer solution or the basicpolymer solution. A preferable concentration of the salt is 0.1 to 2.0%by mass. As the concentration of the salt is increased, a polymerelectrolyte forms a more spherical space structure. When theconcentration is too high, however, the polymer electrolyte does notdeposit well on the molding surface, even if the polymer electrolytedeposits. A more preferable concentration of the salt is 0.7 to 1.3% bymass.

One of the other preferable aspects of the production method of themedical device of the present invention is a method further includingthe following step 5:

<Step 5>

forming the layer made of the acidic polymer and the basic polymer onthe molding by the previous step, and thereafter irradiating the moldingwith radiation rays.

The irradiation of the radiation rays may be carried out in a state ofimmersing the molding into the coating liquid or may be carried outafter the molding is pulled out from the coating liquid and washed. Inaddition, the irradiation of the radiation rays is preferably carriedout in the state of immersing the molding in a liquid other than thecoating liquid. This case is preferable because the radiation rays moreeffectively affect. In this case, as a solvent for the liquid used forimmersing the coated molding, various types of organic and inorganicsolvents are applicable and are not particularly limited. By way ofexample, water; various alcohol-based solvents such as methanol,ethanol, propanol, 2-propanol, butanol, tert-butanol, tert-amyl alcohol,and 3,7-dimethyl-3-octanol; various aromatic hydrocarbon solvents suchas benzene, toluene, and xylene; various aliphatic hydrocarbon solventssuch as hexane, heptane, octane, decane, petroleum ether, kerosene,ligroin and paraffin; various ketone-based solvents such as acetone,methylethyl ketone, and methylisobutyl ketone; various ester-basedsolvents such as ethyl acetate, butyl acetate, methyl benzoate, dioctylphthalate, and ethylene glycol diacetate; diethyl ether,tetrahydrofuran, dioxane, and various glycol ether-based solvents suchas ethylene glycol dialkyl ether, diethylene glycol dialkyl ethers,triethylene glycol dialkyl ether, tetraethylene glycol dialkyl ethers,polyethylene glycol dialkyl ethers, a polyethylene glycol-polypropyleneglycol block copolymer, and a polyethylene glycol- and polypropyleneglycol random copolymer are included, and these solvents can be usedsingly or by mixing. Among them, the most preferable is water. When themolding in a state of being immersed in a water-based liquid isirradiated with the radiation rays, physiologic saline, phosphoricacid-based buffer solution (preferably a pH of 7.1 to 7.3), and boricacid-based buffer solution (preferably a pH of 7.1 to 7.3), other thanpure water are preferable as water-based liquids.

If the molding is irradiated with the radiation rays in a state of beingenclosed in a sealed container, there is an advantage that the moldingis simultaneously sterilized.

As the radiation ray, γ ray is preferably used. In this case, when aradiation dose of irradiated γ ray is too small, sufficient bondingbetween the molding and the coating layer is not obtained, whereas, whenthe radiation dose is too large, physical properties of the molding isdeteriorated, and therefore, the radiation dose is preferably 0.1 to 100kGy, more preferably 15 to 50 kGy, and most preferably 20 to 40 kGy. Bythis irradiation, at least a part of inside of the coating layer and atleast a part between the coating layer and the molding are crosslinked,and therefore, durability of the coating layer (for example, durabilityfor washing by rubbing) can be improved.

The medical device of the present invention is useful for softophthalmic lenses, particularly, ophthalmic lenses such as a softcontact lens, an intraocular lens, an artificial cornea, a cornealinlay, a corneal onlay, and spectacle lenses. Among them, medical deviceis particularly preferable for the soft contact lens.

EXAMPLES

Hereinafter, the present invention will be specifically described withreference to Examples. The present invention, however, is not limited toExamples.

(Analysis Method and Evaluation Method)

In this specification, a wet state means a state in which a sample isimmersed in pure water or a borate buffer solution at room temperature(25° C.) for 24 hours or more. After the sample is taken out from purewater or the borate buffer solution, the measurement of physicalproperties in the wet state is carried out as soon as possible.

In this specification, a dry state means a state in which a wet statesample is dried under vacuum at 40° C. for 16 hours. A degree of vacuumin the vacuum drying is set to 2 hPa or less. After the vacuum drying,measurement of physical properties in the dry state is carried out assoon as possible.

In this specification, a borate buffer solution is a “salt solution”described in Example 1 of Japanese Translation of PCT Application No.2004-517163, the disclosure of which is incorporated herein byreference. Specifically, the borate buffer solution is made bydissolving 8.48 g of sodium chloride, 9.26 g of boric acid, 1.0 g ofsodium borate (sodium tetraborate decahydrate), and 0.10 gethylenediamine tetraacetic acid into pure water to prepare 1000 mL ofan aqueous solution.

(1) Molecular Weight

If not otherwise specified, a mass average molecular weight and a numberaverage molecular weight are measured by a GPC method under thefollowing conditions.

Pump: DP-8020 manufactured by TOSOH CORPORATION

Detector: RI-8010 manufactured by TOSOH CORPORATION

Column oven: CTO-6A manufactured by Shimadzu Corporation

Autosampler: AS-8010 manufactured by TOSOH CORPORATION

Column: TSKgeI GMHHR-M (inner diameter 7.8 mm×30 cm, particle size 5μm)×2, manufactured by TOSOH CORPORATION

Column temperature: 35° C.

Mobile phase: Chloroform

Flow rate: 1.0 mL/min

Sample concentration: 0.4% by mass

Injection volume: 100 μL

Standard sample: Polystyrene (molecular weight 1010 to 1090000)

(2) Wettability

A contact lens-shaped test specimen was immersed in the borate buffersolution in a beaker at room temperature for 24 hours or more. Thebeaker containing the borate buffer solution and the test specimen wassubjected to an ultrasonic cleaner (1 minute). The test specimen waspulled out from the borate buffer solution and surface appearance at thetime of holding the test specimen in the air so as to set a diameterdirection perpendicular was visually observed, and the surfaceappearance was determined according to the following criteria. Here, thediameter is a diameter of a circle formed by the edge of the contactlens.

A: A liquid film on the surface was retained for more than 20 seconds.

B: A liquid film on the surface was broken from 10 seconds or more toless than 20 seconds.

C: A liquid film on the surface was broken from 5 seconds or more toless than 10 seconds.

D: A liquid film on the surface was broken from 1 second or more to lessthan 5 seconds.

E: A liquid film on the surface was broken in a moment (less than 1second).

(3) Lubricity

The lubricity was measured by a sensitive evaluation when a sample (in acontact lens shape) in the wet state with the borate buffer solution wasrubbed five times with human fingers.

A: The sample had extremely excellent lubricity.

B: The sample had lubricity about in the middle of A and B.

C: The sample had medium lubricity.

D: The sample had almost no lubricity (about in the middle of C and E).

E: The sample had no lubricity.

(4) Mucin Adhesion

As the mucin, Mucin, Bovine Submaxillary Gland manufactured byCALBIOCHEM CORPORATION (Catalog No. 499643) was used. The contactlens-shaped sample was immersed in a mucin aqueous solution having aconcentration of 0.1% by mass under conditions of 37° C. for 20 hours,and thereafter, an amount of mucin adhering to the sample wasquantitatively determined by a BCA (bicinchoninic acid) protein assaymethod.

(5) Lipid Adhesion

A stirring bar (36 mm) was placed into a 500 ml of beaker, and then 1.5g of methyl palmitate and 500 g of pure water were charged. Atemperature of a water bath was set to 37° C.; the above beaker wasplaced at the center of the water bath; and the mixture was stirred witha magnetic stirrer for 1 hour. A rotation speed was set to 600 rpm. Thecontact lens-shaped samples were placed one by one in a lens basket andthe basket was placed in the above beaker to stir without modification.One hour later, stirring was stopped and the samples in the lens basketwere washed by rubbing with water of 40° C. and a liquid householddetergent (“Mamalemon (registered trademark)”, manufactured by LionCorporation). The samples after washing were placed into a screw tubecontaining the borate buffer solution (pH 7.1 to 7.3) and the screw tubewas immersed into an ice bath for 1 hour. After the screw tube was takenout from the ice bath, white turbidity of the sample was visuallyobserved and an adhesion amount of methyl palmitate to the sample wasdetermined by the following criteria.

A: The sample had no white turbidity and was clear.

B: The sample had white turbidity in few parts.

C: The sample had white turbidity in many parts.

D: The sample had white turbidity in almost all parts.

E: The sample entirely had white turbidity.

(6) Immersion Test into Artificial Lacrimal Fluid

As an artificial lacrimal fluid, a tear-like fluid (TLF) buffer solutionwas prepared according to a method described in WO 2008/127299, thedisclosure of which is incorporated herein by reference, page 32, lines5 to 36, except that oleic acid was used instead of oleic acid propylester. In one well in a multi-plate for culture (24-well type, materialpolystyrene, radiation sterilized), 2 ml of the artificial lacrimalfluid is poured and a piece of sample (a contact lens shape) wasimmersed. The multi-plate was shaken at 100 rpm at 37° C. for 24 hours.Thereafter, the sample was taken out, and after the sample was lightlywashed with a phosphate buffer solution (PBS), the sample was immersedinto the well in which 2 ml of the lacrimal fluid was replaced. Afterthe multi-plate was further shaken at 100 rpm at 37° C. for 24 hours,the sample was lightly washed with PBS and an amount of adheringsubstance was observed by visually evaluating a degree of whiteturbidity of the sample. The evaluation was carried out based on thefollowing criteria.

A: No white turbidity was observed.

B: The sample had white turbidity in few parts (less than 10% in termsof area).

B: The sample had white turbidity in many parts (10% to 50% in terms ofarea).

D: The sample had white turbidity in almost all parts (50% to 100% interms of area), but the backside was seen through the sample.

E: The sample entirely had thick white turbidity, and the backside wasdifficult to be seen through the sample.

(7) Dynamic Contact Angle Measurement

The dynamic contact angle was measured with a sample in the wet statewith the borate buffer solution using a dynamic wettability testerWET-6000 manufactured by RHESCA Corporation Limited. As a dynamiccontact angle sample, a film-shaped test specimen having a size of about5 mm×10 mm×0.1 mm that is cut out from a sample formed in a film shapeor a strip-shaped specimen having a width of 5 mm that is cut out from acontact lens-shaped sample was used to measure a dynamic contact angleto the borate buffer solution at the time of advance. An immersion ratewas set to 0.1 mm/sec and an immersion depth was set to 7 mm.

(8) Water Content

A test specimen having a contact lens shape was used. After the testspecimen was immersed in the borate buffer solution and left to stand atroom temperature for 24 hours or more, the water adhering to the surfacewas wiped off with a wiping cloth (“Kimwipe (registered trademark)”manufactured by NIPPON PAPER CRECIA Co., LTD.) to measure a mass (Ww).Thereafter, the test specimen was dried with a vacuum dryer at 40° C.for 16 hours to measure a mass (Wd). The water content was calculatedfrom the following formula. When the obtained value was less than 1%,the value was determined to be equal to or less than measurement limitand represented as “less than 1%”.Water content (%)=100×(Ww−Wd)/Ww

(9) Total Light Transmittance

The total light transmittance was measured using SM Color Computer(model SM-7-CH, manufactured by Suga Test Instruments Co., Ltd.). Thewater on the lens-shaped sample was lightly wiped off and the totallight transmittance was measured by setting the sample in an opticalpath. A thickness was measured using ABC Digimatic Indicator (ID-C112,manufactured by Mitutoyo Corporation) and the sample having thethickness of 0.14 to 0.15 mm was used for measurement.

(10) Tensile Modulus and Tensile Elongation (Elongation at Break)

These properties were measured using a sample in the wet state by theborate buffer solution. A test specimen having a width (a minimum part)of 5 mm, a length of 14 mm, and a thickness of 0.2 mm was cut out fromthe contact lens-shaped sample using a specific cutting die. A tensiletest was carried out using the test specimen with Tensilon Type RTM-100manufactured by Orientec Co., Ltd. A tensile speed was 100 mm/minute anda distance between grips (an initial value) was 5 mm.

(11) Scrubbing Resistance

A depressed area is made in the center of a palm and a sample (a contactlens shape) in the wet state with the borate buffer solution was placedin the depressed area. A wash fluid (“Renu (registered trademark)”Bausch & Lomb Incorporated) was added to the depressed area and each ofthe front surface and the back surface was rubbed 10 times by the ballof the index finger of the other hand. Thereafter, the both surfaces ofthe sample were rubbed 20 times with the sample being clamped by thethumb and the index finger and the wash fluid being poured. The sampleafter washing by rubbing was immersed into the borate buffer solution.Thereafter, the lubricity (3) was evaluated.

(Preparation of Molding)

Reference Example 1 Polydimethylsiloxane Having Methacryloyl Groups atBoth Ends Represented by the Following Formula (M2)

(FM7726, Chisso Corporation, mass average molecular weight 29 kD, numberaverage molecular weight 26 kD) (50 parts by mass) as the component A,trifluoroethyl acrylate (Viscoat 3F, Osaka Organic Chemical IndustryLtd.) (45 parts by mass) as the component B, 2-ethylhexyl acrylate(2-EHA, 3 parts by mass) as the component C, N,N-dimethylaminoethylacrylate (DMAEA, 1 part by mass) as the component C, an ultravioletabsorber having a polymerizable group (RUVA-93, Otsuka Chemical Co.,Ltd.) (1 part by mass) as the component Ck,

a colorant having a polymerizable group represented by the followingestimated structural formula (C3H)

[a colorant made by treating Uniblue A (Sigma-Aldrich Corporation) withhydrochloric acid](0.04 parts by mass) as the component Ck, apolymerization initiator “Irgacure (registered trademark)” 819 (CibaSpecialty Chemicals Inc., 0.75 parts by mass), and t-amyl alcohol (10parts by mass) as a solvent were mixed and stirred. Insoluble matter wasremoved by filtering the mixture with a membrane filter (0.45 μm) toobtain a monomer mixture. This monomer mixture was poured into a testtube and degassed under a reduced pressure of 20 Torr (27 hPa) whilestirring using a touch mixer, and thereafter, the pressure was returnedto atmospheric pressure with argon gas. This operation was repeatedthree times. In a glove box under nitrogen atmosphere, the monomercomposition was filled in a cavity of a mold for a contact lens made ofclear resin (poly 4-methylpentene-1) and polymerized by a lightirradiation (8000 lux, 20 minutes) using fluorescent lamps (TOSHIBACORPORATION FL-6D, daylight color, 6 W, four lamps). After thepolymerization, the mold containing the molded polymer was immersed into60% by mass isopropyl alcohol aqueous solution, and thereby, a moldinghaving a contact lens shape was peeled off from the mold. The obtainedmolding was immersed into a large excess amount of 80% by mass isopropylalcohol aqueous solution at 60° C. for 2 hours. Furthermore, the moldingwas immersed into a large excess amount of 50% by mass isopropyl alcoholaqueous solution at room temperature for 30 minutes, and then immersedinto a large excess amount of 25% by mass isopropyl alcohol aqueoussolution at room temperature for 30 minutes, and then immersed into alarge excess amount of pure water at room temperature for 30 minutes.Finally, the molding was placed in a sealed vial container in a state ofimmersing into clean pure water, and sterilized in an autoclave at 121°C. for 30 minutes. The obtained molding had an edge part diameter ofabout 14 mm and a thickness at the center part of about 0.07 mm. Theobtained molding had a water content of less than 1%, a tensile modulusof 0.614 MPa, and an elongation at break of 593%, was clear, and had noturbidity, and thus, was suitable for a contact lens. In addition, asimilar operation was carried out using two glass plates and a gasket asa mold to obtain a film-like sample of 60 mm×60 mm×0.25 mm.

Reference Example 2

A silicone monomer (13.4 parts by mass) represented by the followingformula (t3)

as the component S, a silicone monomer (36.6 parts by mass) representedby the following formula (t4)

as the component S, N,N-dimethylacrylamide (37 parts by mass) as thehydrophilic component H, 2-hydroxyethyl methacrylate (9.2 parts by mass)as the hydrophilic component H, triethylene glycol dimethacrylate (1.26parts by mass) as the cross-linkable component I, an ultravioletabsorber having a polymerizable group (RUVA-93, Otsuka Chemical Co.,Ltd.) (1.26 parts by mass) as the component Ck, a colorant having apolymerizable group [Uniblue A, Sigma-Aldrich Corporation] (0.02 partsby mass) as the component Ck, a photoinitiator Irgacure 1850 (1.26 partsby mass), and tetrahydrolinalool (23.9 parts by mass) as a solvent weremixed and stirred. A homogeneous and clear monomer composition wasobtained. The monomer composition was degassed under argon atmosphere.In a glove box under nitrogen atmosphere, the monomer composition wasfilled in a cavity of a mold having a lens shape and a lens was obtainedby light irradiation (TOSHIBA CORPORATION FLED, 8.4 kilolux, 20minutes). After the obtained lens was immersed into 60% IPA aqueoussolution at 60° C. for 30 minutes and released from the mold, impuritiessuch as remaining monomers were extracted by immersing the lens into 80%IPA aqueous solution at 60° C. for 2 hours and the lens was hydrated byimmersing each liquid of 50% IPA aqueous solution, 25% IPA aqueoussolution, and water, in which IPA concentrations were decreasedstepwise, for about 30 minutes. The lens was immersed into the boratebuffer solution (pH 7.1 to 7.3) in a 5 mL vial container, and the vialcontainer was placed in an autoclave to carry out boiling treatment at120° C. for 30 minutes. The obtained lens had an edge part diameter ofabout 14 mm and a thickness at the center part of about 0.07 mm. Theobtained lens had a silicon atom content of 12.3%, a water content of41.7%, a tensile modulus of 0.665 MPa, and a total light transmittanceof 84.2%, was clear, and had no turbidity, and thus, was suitable for acontact lens.

(Synthesis of Polymer for Coating)

Synthesis Examples of copolymers provided for coating in Examples aredescribed, and, in Synthesis Examples, molecular weights of eachcopolymer were measured under conditions described below.

GPC measurement conditions of the polymer for coating are as follows.

Equipment: Prominence GPC System manufactured by Shimadzu Corporation

Pump: LC-20AD

Autosampler: SIL-20AHT

Column oven: CTO-20A

Detector: RID-10A

Column: GMPWXL (inner diameter 7.8 mm×30 cm, particle size 13 μm),manufactured by TOSOH CORPORATION

Solvent: Water/methanol=1/1 (0.1 N lithium nitrate is added)

Flow rate: 0.5 mL/min

Measurement time: 30 minutes

Sample concentration: 0.1% by mass

Injection volume: 100 μL

Standard sample: Polyethylene oxide standard sample (0.1 kD to 1258 kD)manufactured by Agilent.

Synthesis Example 1 CPHDA: 2-hydroxyethylmethacrylate/N,N-dimethylacrylamide/acrylic acid (a molar ratio of1/2/1)

Into a 200 mL three-necked flask, 2-hydroxyethyl methacrylate (3.25 g,0.025 mol) as the monomer having a hydroxy group, N,N-dimethylacrylamide(4.96 g, 0.050 mol) as the monomer having an amide group, acrylic acid(1.80 g, 0.025 mol) as the acidic monomer, dimethylsulfoxide (41.0 g) asa solvent, and a polymerization initiator VA-061 (Wako Pure ChemicalIndustries, Ltd., 0.008 g, 0.031 mmol) were added, and the three-neckedflask was equipped with a three-way cock, a reflux condenser, athermometer, and a mechanical stirrer. A monomer concentration was 20%by mass.

After inside of the three-necked flask was degassed with a vacuum pumpand argon replacement was carried out for 3 times, the mixture wasstirred at 60° C. for 0.5 hours, and thereafter, the temperature wasraised to 70° C. and the mixture was stirred for 4.5 hours. Aftercompletion of the polymerization, the polymerization reaction liquid wascooled to room temperature and the liquid was poured to 50 mL of ethylacetate and the obtained mixture was left to stand for one night. In thenext day, a supernatant liquid was removed by decantation. The obtainedsolid content was washed 10 times with methanol/n-hexane=8 mL/40 mL. Thesolid content was dried at 60° C. for one night with a vacuum drier.After liquid nitrogen was poured to the solid content and the solidcontent was fragmentized with a spatula, the solid content was dried at60° C. for 3 hours with a vacuum drier. Molecular weights of thusobtained copolymer were a Mn of 123 kD and a Mw of 428 kD (Mw/Mn=3.48).

Synthesis Example 2 CPHDA: 2-hydroxyethylmethacrylate/N,N-dimethylacrylamide/acrylic acid (a molar ratio of1/2/1)

Into a 200 mL three-necked flask, 2-hydroxyethyl methacrylate (3.25 g,0.025 mol) as the monomer having a hydroxy group, N,N-dimethylacrylamide(4.96 g, 0.050 mol) as the monomer having an amide group, acrylic acid(1.80 g, 0.025 mol) as the acidic monomer, dimethylsulfoxide (41.0 g) asa solvent, a polymerization initiator VA-061 (Wako Pure ChemicalIndustries, Ltd., 0.016 g, 0.062 mmol), and 2-mercaptoethanol (2-ME, 14μL, 0.2 mmol) were added, and the three-necked flask was equipped with athree-way cock, a reflux condenser, a thermometer, and a mechanicalstirrer. A monomer concentration was 20% by mass. After inside of thethree-necked flask was degassed with a vacuum pump and argon replacementwas carried out for 3 times, the mixture was stirred at 60° C. for 0.5hours, and thereafter, the temperature was raised to 70° C. and themixture was stirred for 4.5 hours. After completion of thepolymerization, the polymerization reaction liquid was cooled to roomtemperature and the liquid was poured to 50 mL of ethyl acetate and theobtained mixture was left to stand for one night. In the next day, asupernatant liquid was removed by decantation. The obtained solidcontent was washed 10 times with methanol/n-hexane=8 mL/40 mL. The solidcontent was dried at 60° C. for one night with a vacuum drier. Afterliquid nitrogen was poured to the solid content and the solid contentwas fragmentized with a spatula, the solid content was dried at 60° C.for 3 hours with a vacuum drier. Molecular weights of thus obtainedcopolymer were a Mn of 49 kD and a Mw of 103 kD (Mw/Mn=2.11).

Synthesis Example 3 CPHDA: 2-hydroxyethylmethacrylate/N,N-dimethylacrylamide/acrylic acid (a molar ratio of1/2/1)

Into a 200 mL three-necked flask, 2-hydroxyethyl methacrylate (3.25 g,0.025 mol) as the monomer having a hydroxy group, N,N-dimethylacrylamide(4.96 g, 0.050 mol) as the monomer having an amide group, acrylic acid(1.80 g, 0.025 mol) as the acidic monomer, dimethylsulfoxide (41.0 g) asa solvent, a polymerization initiator VA-061 (Wako Pure ChemicalIndustries, Ltd., 0.016 g, 0.062 mmol), and 2-mercaptoethanol (2-ME, 43μL, 0.62 mmol) were added, and the three-necked flask was equipped witha three-way cock, a reflux condenser, a thermometer, and a mechanicalstirrer. A monomer concentration was 20% by mass. After inside of thethree-necked flask was degassed with a vacuum pump and argon replacementwas carried out for 3 times, the mixture was stirred at 60° C. for 0.5hours, and thereafter, the temperature was raised to 70° C. and themixture was stirred for 4.5 hours. After completion of thepolymerization, the polymerization reaction liquid was cooled to roomtemperature and the liquid was poured to 500 mL of ethyl acetate and theobtained mixture was left to stand for one night. In the next day, asupernatant liquid was removed by decantation. The obtained solidcontent was washed 10 times with methanol/n-hexane=5 mL/50 mL. The solidcontent was dried at 60° C. for one night with a vacuum drier. Afterliquid nitrogen was poured to the solid content and the solid contentwas fragmentized with a spatula, the solid content was dried at 60° C.for 3 hours with a vacuum drier. Molecular weights of thus obtainedcopolymer were a Mn of 22 kD and a Mw of 42 kD (Mw/Mn=1.89).

Synthesis Example 4 CPHDA: 2-hydroxyethylmethacrylate/N,N-dimethylacrylamide/acrylic acid (a molar ratio of2/1/1)

Into a 200 mL three-necked flask, 2-hydroxyethyl methacrylate (6.51 g,0.050 mol) as the monomer having a hydroxy group, N,N-dimethylacrylamide(2.48 g, 0.025 mol) as the monomer having an amide group, acrylic acid(1.80 g, 0.025 mol) as the acidic monomer, dimethylsulfoxide (43.2 g) asa solvent, a polymerization initiator VA-061 (Wako Pure ChemicalIndustries, Ltd., 0.016 g, 0.062 mmol), and 2-mercaptoethanol (2-ME, 43μL, 0.62 mmol) were added, and the three-necked flask was equipped witha three-way cock, a reflux condenser, a thermometer, and a mechanicalstirrer. A monomer concentration was 20% by mass. After inside of thethree-necked flask was degassed with a vacuum pump and argon replacementwas carried out for 3 times, the mixture was stirred at 60° C. for 0.5hours, and thereafter, the temperature was raised to 70° C. and themixture was stirred for 4.5 hours. After completion of thepolymerization, the polymerization reaction liquid was cooled to roomtemperature and the liquid was poured to 500 mL of ethyl acetate and theobtained mixture was left to stand for one night. In the next day, asupernatant liquid was removed by decantation. The obtained solidcontent was washed 10 times with methanol/n-hexane=5 mL/50 mL. The solidcontent was dried at 60° C. for one night with a vacuum drier. Afterliquid nitrogen was poured to the solid content and the solid contentwas fragmentized with a spatula, the solid content was dried at 60° C.for 3 hours with a vacuum drier. Molecular weights of thus obtainedcopolymer were a Mn of 17 kD and a Mw of 33 kD (Mw/Mn=1.98).

Synthesis Example 5 CPHDA: 2-hydroxyethylmethacrylate/N,N-dimethylacrylamide/acrylic acid (a molar ratio of1.5/1.5/1)

Into a 200 mL three-necked flask, 2-hydroxyethyl methacrylate (4.88 g,0.038 mol) as the monomer having a hydroxy group, N,N-dimethylacrylamide(3.72 g, 0.038 mol) as the monomer having an amide group, acrylic acid(1.80 g, 0.025 mol) as the acidic monomer, dimethylsulfoxide (41.6 g) asa solvent, and a polymerization initiator VA-061 (Wako Pure ChemicalIndustries, Ltd., 0.016 g, 0.062 mmol) were added, and the three-neckedflask was equipped with a three-way cock, a reflux condenser, athermometer, and a mechanical stirrer. A monomer concentration was 20%by mass. After inside of the three-necked flask was degassed with avacuum pump and argon replacement was carried out for 3 times, themixture was stirred at 60° C. for 0.5 hours, and thereafter, thetemperature was raised to 70° C. and the mixture was stirred for 4.5hours. After completion of the polymerization, the polymerizationreaction liquid was cooled to room temperature and the liquid was pouredto 50 mL of ethyl acetate and the obtained mixture was left to stand forone night. In the next day, a supernatant liquid was removed bydecantation. The obtained solid content was washed 10 times withmethanol/n-hexane=8 mL/40 mL. The solid content was dried at 60° C. forone night with a vacuum drier. After liquid nitrogen was poured to thesolid content and the solid content was fragmentized with a spatula, thesolid content was dried at 60° C. for 3 hours with a vacuum drier.Molecular weights of thus obtained copolymer were a Mn of 83 kD and a Mwof 319 kD (Mw/Mn=3.85).

Synthesis Example 6 CPDA: N,N-dimethylacrylamide/acrylic acid (a molarratio of 2/1)

Into a 500 mL three-necked flask, N,N-dimethylacrylamide (59.50 g, 0.600mol) as the monomer having an amide group, acrylic acid (21.62 g, 0.300mol) as the acidic monomer, pure water (325.20 g), a polymerizationinitiator VA-061 (Wako Pure Chemical Industries, Ltd., 0.1408 g, 0.562mmol), and 2-mercaptoethanol (43.8 μL, 0.63 mmol) were added, and thethree-necked flask was equipped with a three-way cock, a refluxcondenser, a thermometer, and a mechanical stirrer. A monomerconcentration was 20% by mass. After inside of the three-necked flaskwas degassed with a vacuum pump and argon replacement was repeated for 3times, the mixture was stirred at 50° C. for 0.5 hours, and thereafter,the temperature was raised to 70° C. and the mixture was stirred for 6.5hours. After completion of the polymerization, the polymerizationreaction solution was concentrated to 400 g with an evaporator and themixture was poured into 2-propanol/n-hexane=500 mL/500 mL and was leftto stand, and thereafter, supernatant liquid was removed by decantation.An obtained solid content was washed three times with2-propanol/n-hexane=250 mL/250 mL. The solid content was dried at 60° C.for one night with a vacuum drier. After liquid nitrogen was poured tothe solid content and the solid content was fragmentized with a spatula,the solid content was dried at 60° C. for 3 hours with a vacuum drier. Amolecular weight of thus obtained copolymer was an Mn of 55 kD and an Mwof 192 kD (Mw/Mn=3.5).

(Preparation of Coating Solution)

Hereinafter, pure water represents water purified by filtering with areverse osmosis membrane.

<PEI Solution>

Polyethyleneimine (P3143, Sigma-Aldrich Corporation, a molecular weightof 750000) was dissolved into pure water to prepare 1% by mass aqueoussolution.

<PAA Solution>

Polyacrylic acid (169-18591, Wako Pure Chemical Industries, Ltd., amolecular weight of 250000) was dissolved into pure water to prepare1.2% by mass aqueous solution.

<Solution of Copolymer>

Each of the copolymers obtained in Synthesis Examples listed in Table 1was dissolved in a solvent listed in Table 1 to prepare CPHDA solutionsA to E and a CPDA solution having concentrations listed in Table 1.

TABLE 1 Monomer Monomer having having hydroxy amide Acidic A B CSolution group group monomer (Molar (Molar (Molar Mn Mw concentrationCopolymer (A) (B) (C) ratio) ratio) ratio) (kD) (kD) Solvent (% by mass)CPHDA Synthesis HEMA DMA AA 1 2 1 123 428 Pure 1 solution A Example 1water CPHDA Synthesis HEMA DMA AA 1 2 1 49 103 Pure 1 solution B Example2 water CPHDA Synthesis HEMA DMA AA 1 2 1 22 42 Pure 1 solution CExample 3 water CPHDA Synthesis HEMA DMA AA 2 1 1 17 33 Pure 1 solutionD Example 4 water CPHDA Synthesis HEMA DMA AA 1.5 1.5 1 83 319 Pure 1solution E Example 5 water CPDA Synthesis — DMA AA — 2 1 55 192 Pure 1solution Example 6 water DMA: N,N-dimethylacrylamide HEMA:2-hydroxyethyl methacrylate AA: Acrylic acid

Examples 1 to 10

A layer made of an acidic polymer and a basic polymer (a coating layer)was formed on the moldings obtained in Reference Examples 1 and 2. Eachof the moldings listed in Table 2 was immersed into a first solutionlisted in Table 2 for 30 minutes, and thereafter, immersed into threepure water baths for 5 minutes each. Subsequently, the molding wasimmersed into a second solution listed in Table 2 for 30 minutes, andthereafter, immersed into three pure water baths for 5 minutes each.Subsequently, the molding was immersed into a third solution listed inTable 2 for 30 minutes, and thereafter, immersed into three pure waterbaths for 5 minutes each. With respect to each of the samples on whichthe coating layer was formed, evaluation such as the mucin adhesion andthe lubricity was carried out. The evaluation results are listed inTable 2.

Comparative Examples 1 to 6

The molding obtained in each Reference Example listed in Table 2 wasimmersed into the first solution listed in Table 2 for 30 minutes, andthereafter, immersed into three pure water baths for 5 minutes each.Subsequently, the molding was immersed into the second solution listedin Table 2 for 30 minutes, and thereafter, immersed into three purewater baths for 5 minutes each. Subsequently, the molding was immersedinto the third solution listed in Table 2 for 30 minutes, andthereafter, immersed into three pure water baths for 5 minutes each. Theobtained evaluation results are listed in Table 2. In Table 2, “−” meansthat treatment by each polymer solution was not carried out (ComparativeExample 1 is a base material to which treatment with the first to thethird solutions were not carried out, that is, on which the coatinglayer was not formed).

TABLE 2 Immersion Dynamic test into Molding Mucin contact artificialDurability used for First Second Third adhesion Slipper- Wetta- anglelacrimal Lipid to washing coating solution solution solution (μg/cm²)iness bility (advance) fluid adhesion by rubbing Example 1 Reference PAAPEI CPHDA 1.95 A B 69 D C C Example 1 solution solution solution AExample 2 Reference PAA PEI CPHDA 1.87 A B 60 C B C Example 1 solutionsolution solution B Example 3 Reference PAA PEI CPHDA 1.97 A B 88 C C CExample 1 solution solution solution C Example 4 Reference PAA PEI CPHDA1.81 A B 73 D C C Example 1 solution solution solution D Example 5Reference PAA PEI CPHDA 1.92 A B 58 C C C Example 1 solution solutionsolution E Example 6 Reference PAA PEI CPHDA 10.79 A C 78 E A C Example2 solution solution solution A Example 7 Reference PAA PEI CPHDA 6.82 AC 61 E A C Example 2 solution solution solution B Example 8 ReferencePAA PEI CPHDA 20.79 C C 90 E A C Example 2 solution solution solution CExample 9 Reference PAA PEI CPHDA 7.58 A C 68 E A C Example 2 solutionsolution solution D Example 10 Reference PAA PEI CPHDA 8.95 C C 60 E A CExample 2 solution solution solution E Comparative Reference — — — 1.51E E 118 E C E Example 1 Example 1 Comparative Reference PAA PEI PAA 2.89A A 36 E D C Example 2 Example 1 solution solution solution ComparativeReference PAA PEI CPDA 2.53 A A 76 E D C Example 3 Example 1 solutionsolution solution Comparative Reference — — — 3.86 E E 106 D E E Example4 Example 2 Comparative Reference PAA — — 11.08 A A 34 E D C Example 5Example 2 solution Comparative Reference PAA PEI PAA 5.14 B B 72 E B CExample 6 Example 2 solution solution solution

In the case of the low water content base materials prepared inReference Example 1 (Examples 1 to 5), medical devices having excellentwettability and lubricity, and reducing the mucin adhesion, theartificial lacrimal fluid adhesion, and the lipid adhesion wereobtained. When the water-containing base materials in Reference Example2 were used (Examples 6 to 10), medical devices having adequatewettability and lubricity, and excellent lipid adhesion resistance wereobtained.

Comparative Example 7

After the lens obtained in Reference Example 1 was immersed into 1% bymass PVP K90 aqueous solution (polyvinylpyrrolidone, Sigma-Aldrich JapanK. K., a molecular weight of 360000) at room temperature for 30 minutes,the lens was taken out and touched with a human finger, and as a result,the lens has very excellent lubricity. This lubricity is A in theevaluation criteria of lubricity. Thereafter, the lens is lightly rinsedwith pure water in a beaker, and touched with the human finger, and as aresult, the lens has no lubricity. This lubricity is E in the evaluationcriteria of lubricity.

Comparative Example 8

After the lens obtained in Reference Example 2 was immersed into 1% bymass PVP K90 aqueous solution (polyvinylpyrrolidone, Sigma-Aldrich JapanK. K., a molecular weight of 360000) at room temperature for 30 minutes,the lens was taken out and touched with human fingers, and as a result,the lens has very excellent lubricity. This lubricity was A in theevaluation criteria of lubricity. Thereafter, the lens was lightlyrinsed with pure water in a beaker, and touched with human fingers, andas a result, the lens has no lubricity. This lubricity was E in theevaluation criteria of lubricity.

The present invention relates to the medical device, and is suitablyemployed for a device, for example, an ophthalmic lens or a material forskin, that is used by being in contact with a patient or a tissue takenfrom a patient such as blood or other body fluids. Particularly, themedical device is useful as, soft ophthalmic lenses, for example,ophthalmic lenses such as a soft ophthalmic lens, for example, a softcontact lens, an intraocular lens, an artificial cornea, a cornealinlay, a corneal onlay, and spectacle lenses.

REFERENCE SIGNS LIST

-   -   1 Apparatus    -   10 Sample Stage    -   10 a Quartz Glass Plate    -   11 Measuring Jig (made of aluminum)    -   12 Friction Detection Part    -   13 Force Measuring Device    -   20 Friction Element    -   21 Mounting Holder (made of aluminum)    -   22 Gasket (made of “Teflon (registered trademark)”)    -   23 Nut (made of aluminum)    -   S Sample

The invention claimed is:
 1. A medical device comprising: one or morelayers comprising an acidic polymer and one or more layers comprising abasic polymer formed on at least a part of a surface of a base material,wherein at least one of an acidic polymer and a basic polymer formingthe one or more layers is a multi-component copolymer of three or morecomponents.
 2. The medical device according to claim 1, wherein the oneor more layers are formed by carrying out treatment with one or moreacidic polymer solutions one or more times and carrying out treatmentwith one or more basic polymer solutions one or more times.
 3. Themedical device according to claim 1, wherein the one or more layers areformed by carrying out treatment with an acidic polymer solution one ortwo times and carrying out treatment with a basic polymer solution oneor two times, and consequently carrying out the treatment three times intotal.
 4. The medical device according to claim 1, wherein at least oneof the acidic polymer and the basic polymer forming the one or morelayers is a polymer having a group selected from a hydroxy group and anamide group.
 5. The medical device according to claim 1, wherein themulti-component copolymer of three or more components comprises one ormore of each of an acidic monomer or a basic monomer, a monomer having ahydroxy group, and a monomer having an amide group.
 6. The medicaldevice according to claim 5, wherein the acidic monomer comprises atleast one of an acidic group selected from a carboxy group, a sulfonicacid group, and a phosphoric acid group in a molecule thereof.
 7. Themedical device according to claim 5, wherein the basic monomer comprisesan amino group.
 8. The medical device according to claim 1, wherein thebase material is a low water content base material having a watercontent of 10% by mass or less.
 9. The medical device according to claim1, wherein the base material comprises a polymer of the followingcomponent A or a copolymer of the following component A and component Bas a main component: Component A: a polysiloxane compound having aplurality of polymerizable functional groups per molecule and a numberaverage molecular weight of 6000 or more; and Component B: apolymerizable monomer having a fluoroalkyl group.
 10. The medical deviceaccording to claim 9, wherein the component A is a polysiloxane compoundrepresented by the following formula (A1):

where X¹ and X² each independently represents a polymerizable functionalgroup; R¹ to R⁸ each independently represents a substituent selectedfrom hydrogen, an alkyl group having a carbon number of 1 to 20, aphenyl group, and a fluoroalkyl group having a carbon number of 1 to 20;L¹ and L² each independently represents a divalent group; a and b eachindependently represents an integer of 0 to 1500; and a and b are notzero at the same time.
 11. The medical device according to claim 1,wherein the base material is a hydrogel.
 12. The medical deviceaccording to claim 11, wherein the base material is a silicone hydrogelcontaining 5% by mass or more of silicon atoms.
 13. The medical deviceaccording to claim 1, wherein the medical device is a soft ophthalmiclens.
 14. A method for producing a medical device comprising step 1 tostep 3 in this order, wherein any one of an acidic polymer and a basicpolymer used in the step 2 or 3 is a multi-component copolymer of threeor more components, the method comprising: the step 1 of polymerizing amixture comprising a monomer having a siloxanyl group to obtain amolding; the step 2 of contacting the molding to a basic polymersolution, and thereafter, washing and removing the excessive basicpolymer solution; and the step 3 of contacting the molding, which hasbeen treated with the basic polymer solution of the step 2, to an acidicpolymer solution, and thereafter, washing and removing the excessiveacidic polymer solution.
 15. A method for producing a medical devicecomprising step 1 to step 4 in this order, wherein any one of an acidicpolymer and a basic polymer used in the steps 2 to 4 is amulti-component copolymer of three or more components, the methodcomprising: the step 1 of polymerizing a mixture comprising a monomerhaving a siloxanyl group to obtain a molding; the step 2 of contactingthe molding to an acidic polymer solution, and thereafter, washing andremoving the excessive acidic polymer solution; the step 3 of contactingthe molding, which has been treated with the acidic polymer solution ofthe step 2, to a basic polymer solution, and thereafter, washing andremoving the excessive basic polymer solution; and the step 4 ofcontacting the molding, which has been treated with the acidic polymersolution of the step 2 and the basic polymer solution of the step 3, toan acidic polymer solution being the same as or different from theacidic polymer in the step 2, and thereafter, washing and removing theexcessive acidic polymer solution.